Inflammatory diseases

SPECIFICALLY meso-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PHOTODYNAMIC THERAPY (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, opthamological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. In other embodiments the nucleophilic substitution on pentafluorophenyl-substituted tetrapyrroles is used to obtain compounds with a high PDT-efficacy. In another embodiment substituents are identified that via their steric and/or electronic influence direct the dihydroxylation or reduction with diimine so that one isomer is favored. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.</p>
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PURINONE COMPOUNDS AS KINASE INHIBITORS (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
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UREA DERIVATIVES AND USES THEREOF (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention provides novel compounds of any one of Formulae (I)-(III), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="145.54mm" wi="64.60mm" file="US20180037572A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED PYRIMIDINE COMPOUNDS AS PHOSPHATIDYLINOSITOL 3-KINASE DELTA INHIBITOR AND USE THEREOF (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention belongs to the field of medicinal chemistry, and relates to substituted pyrimidine compounds as phosphatidylinositol 3-kinase (PI3K) δ inhibitor and a use thereof. In particular, the present invention provides a compound as shown by formula I or an isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, the preparation methods of same and pharmaceutical compositions containing these compounds and a use of these compounds or compositions for treating cancer, hyperblastosis diseases or inflammatory diseases. The compounds of the present invention have a good inhibiting activity on PI3Kδ and have a high selectivity. It is hoped that these will be therapeutic agents for cancer, hyperblastosis diseases or inflammatory diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.03mm" wi="66.46mm" file="US20180037576A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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UREA DERIVATIVES AND USES THEREOF (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention provides novel compounds of any one of Formulae (I)-(III), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="126.24mm" wi="63.50mm" file="US20180037573A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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LIPID-SUBSTITUTED AMINO 1,2-AND 1,3-DIOL COMPOUNDS AS MODULATORS OF TLR2 DIMERIZATION (Fri, 09 Feb 2018)
The present invention relates to lipid-substituted amino 1,2- and 1,3-diol compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins.
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MODIFICATIONS OF THERAPEUTIC AGENTS FOR ENHANCED DELIVERY TO TARGET SITES (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.</p>
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Novel Formulations of a Bruton's Tyrosine Kinase Inhibitor (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including novel pharmaceutical formulations thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
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Nanostructure Enhanced Targeting (NSET) of Inflammatory Cells (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention provides nanomaterials for the specific targeting of immune cells. Methods of treating cardiac disease and inflammatory disease are also described.</p>
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INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are describeded, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
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SUBSTITUTED IMIDAZO[1,5-a]PYRAZINES AS CGRP RECEPTOR ANTAGONISTS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The disclosure generally relates to the novel compounds of formula I, including pharmaceutically acceptable salts, which arc CGRP-receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.73mm" wi="30.82mm" file="US20180030057A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED THIAZOLO-PYRIDINE COMPOUNDS AS MALT1 INHIBITORS (Fri, 02 Feb 2018)
Disclosed are compounds of the general formula (I), wherein R1-R3 are as defined herein, for use as MALT1 inhibitors in the treatment of autoimmune and inflammatory diseases or disorders. Methods of synthesizing the compounds are also disclosed. Also disclosed are pharmaceutical compositions containing a compound of the invention and a method of treating a patient for an autoimmune or an inflammatory disease or disorder, for example, a cancer, by administering a compound of the invention.
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PROCESSES FOR PREPARING JAK INHIBITORS AND RELATED INTERMEDIATE COMPOUNDS (Thu, 25 Jan 2018)
The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3- d ]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3- d ]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.
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OPTIMISED COMBINATION THERAPY AND USE THEREOF TO TREAT CANCER AND AUTOIMMUNE DISEASE (Thu, 25 Jan 2018)
Provided is a series of new poly-fluorosubstituted pyrazolopyrimidine compounds or salts. The compounds are Bruton's tyrosine kinase (BTK) inhibitors. The compounds have better kinase inhibition selectivity and pharmokinetic properties. Also provided is a preparation method for the compounds. Also provided is a combination therapy including the compounds in combination with another targeted drug composition or another drug. The optimised combination therapy has a cooperative effect, inhibits the existence of a tumour better than a single targeted drug, and causes certain tumours to completely disappear. The optimised combination therapy treats drug resistance and cancer recurrence of a tumour better than a single targeted drug, and the treatment cycle is shorter. The present invention also relates to a combined compound and a pharmaceutical preparation wherein said combined compound acts as an active ingredient, said pharmaceutical preparation being safer at a lower dosage and having a cooperative effect efficacy. Also provided is a method of using the compounds and a preparation thereof to treat and inhibit an autoimmune disease or illness, a heterogeneous autoimmune disease or illness, an inflammatory disease, a cancer or an illness.
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SITE SPECIFIC DOSING OF A BTK INHIBITOR (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Disclosed herein are formulations and methods of site specific administration of Compound (I) or a pharmaceutically acceptable salt thereof. Compound (I) is a potent BTK inhibitor and hence can be useful for the treatment of diseases such as cancer, autoimmune, and inflammatory diseases.</p>
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TGR5 Modulators and Methods of Use Thereof (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The invention relates to compounds of Formula A:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.32mm" wi="70.70mm" file="US20180016295A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, liver disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.</p>
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METHODS FOR TREATING VASCULAR LEAK SYNDROME (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Disclosed are methods for treating Vascular Leak Syndrome. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, inter alia, sepsis, lupus, irritable bowel disease. Yet further disclosed are methods for treating renal cell carcinoma and melanoma. Still further disclosed are methods for reducing metastasis of malignant cells and/or preventing the proliferation of carcinoma cells via spreading due to vascular leakage.</p>
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COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Compounds of formula I defined herein act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for the prevention and/or treatment of broncho-obstructive or inflammatory diseases.</p>
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PYRIMIDINONE DERIVATIVES AND USES THEREOF TO NEUTRALIZE THE BIOLOGICAL ACTIVITY OF CHEMOKINES (Fri, 19 Jan 2018)
A subject of the present invention is a compound having the general formula (I) a pharmaceutically acceptable salt thereof or a tautomeric form thereof, wherein A, B3, B4, B5, Y, X, B1 and B2 are as defined in any one of claims 1 to 10. Another subject of the invention is the compound as defined above for use as a medicament, in particular for preventing and/or treating inflammation and inflammatory diseases, immune and auto-immune diseases, pain related diseases, genetic diseases and/or cancer.
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INHIBITORS OF CYCLIN DEPENDNT KINASE 7 (CDK7) (Fri, 19 Jan 2018)
The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders (Fri, 19 Jan 2018)
The present invention discloses compounds according to Formula I: Wherein R Ia, Ri, R2 , R4 R', R6a, R6', R7, R', W, X, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention. 1ia Rl Rib
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Thu, 18 Jan 2018)
The present invention discloses compounds according to Formula I: Wherein R 1a , R 1b , R 2 , R 4 , R 5 , R 6a , R 6b , R 7 , R 8 , W, X, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.
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HETEROCYCLIC COMPOUNDS AND USE THEREOF (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury, cancer, inflammatory disease, and autoimmune disease with the heterocyclic compounds.</p>
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2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to the technical field of medicinal chemistry, and in particular discloses a 2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof. The compound and pharmaceutically acceptable salt, isomer, racemate, prodrug, co-crystallized complex, hydrate, and solvate thereof can effectively inhibit the BET bromodomain receptor, and can be used for preparing a medicine for treating cancers, cell proliferative disorders, inflammatory diseases, and autoimmune disorders, sepsis, and viral infections.</p>
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INHIBITORS OF TRKA KINASE (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present invention is directed to the compounds of Formula I which are inhibitors of tropomyosin-related kinase A (TrkA): Formula (I) or steroisomers, tautomers or a pharmaceutically acceptable salts, metabolites, isotopes, solvates or prodrugs thereof, wherein, Ra, Rb, Rc, Rd, R1, R2, L and Het-Ar are as defined herein. These compounds can be used for the preventive and/or therapeutic treatment of diseases or disorders associated with abnormal activities of nerve growth factor (NGF) receptor TrkA such as Pain, inflammation or an inflammatory diseases, Cancer, atherosclerosis, restenosis, thrombosis, Neurodegenerative diseases, Erectile Dysfunction (ED), Skin disorders, Autoimmune disease like Multiple sclerosis, Sjögren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, Infectious diseases, diseases related to an imbalance of the regulation of bone remodeling, endometriosis, pelvic pain syndrome and diseases resulting from abnormal tissue remodelling and fibrotic disorders; or a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.13mm" wi="69.85mm" file="US20180009781A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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IMIDAZO[1,2-A]PYRIDINE DERIVATIVES, METHODS FOR PREPARING THE SAME AND USE THEREOF (Fri, 12 Jan 2018)
The present disclosure relates to novel imidazo[1,2-a]pyridine derivatives, and more particularly to imidazo[1,2-a]pyridine derivatives having an excellent activity of inhibiting gastric acid secretion, methods for preparing the same, and the use thereof. The imidazo[1,2-a]pyridine derivatives according to the present disclosure have gastric acid secretion inhibitory activity, and thus may be effectively used for the prevention or treatment of gastrointestinal inflammatory diseases or gastric acid-related diseases.
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SUBSTITUTED PYRIMIDINE COMPOUNDS AS PHOSPHATIDYLINOSITOL 3-KINASE DELTA INHIBITOR AND USE THEREOF (Thu, 11 Jan 2018)
The present invention belongs to the field of medicinal chemistry, and relates to substituted pyrimidine compounds as phosphatidylinositol 3-kinase (PI3K) ´ inhibitor and a use thereof. In particular, the present invention provides a compound as shown by formula I or an isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, the preparation methods of same and pharmaceutical compositions containing these compounds and a use of these compounds or compositions for treating cancer, hyperblastosis diseases or inflammatory diseases. The compounds of the present invention have a good inhibiting activity on PI3K´ and have a high selectivity. It is hoped that these will be therapeutic agents for cancer, hyperblastosis diseases or inflammatory diseases.
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BICYCLIC COMPOUND (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.02mm" wi="67.90mm" file="US20180002322A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.</p>
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NOVEL COMPOUND USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">A novel compound able to inhibit JAK is disclosed, this compound may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6.</p>
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4,6-DIAMINOQUINAZOLINES AS COT MODULATORS AND METHODS OF USE THEREOF (Fri, 05 Jan 2018)
The invention relates to 4,6-diaminoquinazoline derivatives of formula I which are modulators of the Cot (cancer Osaka thyroid) kinase, also known as MAP3K8, EST or Tlp-2, and their use for treating e.g. cancer, diabetes and inflammatory diseases.
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Oxidized Lipids and Methods of Use Thereof (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention is directed to oxidized lipids and pharmaceutical compositions comprising the same. The present invention is also directed to methods of making an oxidized lipid of the invention and to methods of treating or preventing fibrosis or inflammatory diseases or disorders comprising an oxidized lipid of the invention.</p>
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Cyclic Compounds and Uses Thereof (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention generally relates to substituted benzothiophenyl, substituted benzothiazolyl, substituted indolyl and substituted benzoimidazolyl compounds and, more particularly, to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, inflammatory diseases or an autoimmune system disease (e.g., a T-Cell mediated autoimmune disesase).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="64.43mm" file="US20170369470A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TREATMENT OF TH17 MEDIATED INFLAMMATORY DISEASES (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention provides methods and means to reduce inflammation associated with IRF-4, AP-1 and TH17 mediated diseases. In particular, the invention provides methods and means to treat multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and psoriasis and related conditions.</p>
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CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.</p>
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NON-CATALYTIC SUBSTRATE-SELECTIVE P38α-SPECIFIC MAPK INHIBITORS WITH ENDOTHELIAL-STABILIZING AND ANTI-INFLAMMATORY ACTIVITY, AND METHODS OF USE THEREOF (Fri, 29 Dec 2017)
Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.
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DRUG DELIVERY CONJUGATES CONTAINING UNNATURAL AMINO ACIDS AND METHODS FOR USING (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">Described herein are drug delivery conjugates for targeted therapy. In particular, described herein are drug delivery conjugates that include polyvalent linkers comprising one or more unnatural amino acids that are useful for treating cancers and inflammatory diseases.</p>
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INHIBITORS OF ALPHA-AMINO-BETA-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD<sup>+</sup> biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.</p>
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NOVEL COMPOUNDS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">There are provided inter alia compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.98mm" wi="74.25mm" file="US20170362208A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2a</sup>, R<sup>2b</sup>, R<sup>3</sup>, R<sup>4</sup>, L, X, R<sup>5 </sup>and R<sup>6 </sup>are as defined in the description for use in the treatment of inflammatory diseases.</p>
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention discloses compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.28mm" wi="70.53mm" file="US20170362227A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein R<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6a</sup>, R<sup>6b</sup>, R<sup>7</sup>, R<sup>8</sup>, W, X, Cy, and the subscript a are as defined herein.</p> <p id="p-0004" num="0000">The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.</p>
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4,6-SUBSTITUTED-PYRAZOLO[1,5-a]PYRAZINES AS JANUS KINASE INHIBITORS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">Compounds of Formula I: and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of JAK kinase-associated diseases and disorders, such as autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.01mm" wi="59.10mm" file="US20170362240A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHARMACEUTICAL COMPOSITIONS AND THEIR USE FOR TREATMENT OF CANCER AND AUTOIMMUNE DISEASES (Fri, 22 Dec 2017)
Described herein are combination therapies for cancer (such as lymphoid malignancies) and immune diseases (such as autoimmune diseases and inflammatory diseases). The therapies comprise the combined use of inhibitors of BTK, mTOR kinase, and Bcl-2 or their signaling pathways, and immunomodulatory drugs. Also described are pharmaceutical compositions and kits comprising these inhibitors.
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Novel 5-HT2 antagonists (Fri, 22 Dec 2017)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT<sb>2B</sb> receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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Fused bicyclic pyrimidine derivatives and uses thereof (Fri, 22 Dec 2017)
The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDK12, or CDK13) or a lipid kinase such as a phosphatidylinositol- 5 -phosphate 4- kinase (PIP4K) (e.g., ΡΙ5Ρ4Κα, ΡΙ5Ρ4Κβ, or ΡΙ5Ρ4Κγ)) in the subject.
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4,6-pyrimidinylene derivatives and uses thereof (Fri, 22 Dec 2017)
The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDK12, or CDK13) or a lipid kinase such as a phosphatidylinositol- 5 -phosphate 4- kinase (PIP4K) (e.g., ΡΙ5Ρ4Κα, ΡΙ5Ρ4Κβ, or ΡΙ5Ρ4Κγ)) in the subject.
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IL-18 binding molecules (Fri, 22 Dec 2017)
IL-18 participates in both innate and acquired immunity. The bioactivity of IL-18 is negatively regulated by the IL-18 binding protein (IL18BP), a naturally occurring and highly specific inhibitor. This soluble protein forms a complex with free IL-1 8 preventing its interaction with the IL-18 receptor, thus neutralizing and inhibiting its biological activity. The present invention discloses binding molecules, in particular antibodies or fragments thereof, which bind IL-18 and do not bind IL-18 bound to IL-18BP (IL-18/IL-18BP complex). Apart from its physiological role, IL-18 has been shown to mediate a variety of autoimmune and inflammatory diseases. The binding molecules of the inventions may be used as therapeutic molecules for treating IL-18-related autoimmune and inflammatory diseases or as diagnostic tools for characterizing, detecting and/or measuring IL-18 not bound to IL-18BP as component of the total IL-18 pool.
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(5R)-5-[3-[(3S)-4-(4-CHLORO-3-METHOXY-5-METHYL-PHENYL)-3-METHYL-PIPERAZIN-1-YL]- 3-OXO-PROPYL]-5-METHYL-IMIDAZOLIDINE-2,4-DIONE AS ADAMTS 4 AND 5 INHIBITOR FOR TREATING E.G. OSTEOARTHRITIS (Fri, 15 Dec 2017)
The present invention discloses (5R)-5-[3-[(3S)-4-(4-chloro-3-methoxy-5-methyl-phenyl)-3-methyl-piperazin-l-yl]-3-oxo-propyl]-5-methyl-imidazolidine-2,4-dione according to Formula (I). The present invention relates to the compound of formula (I) inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.
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5-[3-[PIPERAZIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS 4 AND 5 INHIBITORS FOR TREATING E.G. OSTEOARTHRITIS (Fri, 15 Dec 2017)
The present invention discloses 5-[3-[piperazin-l-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives according to Formula (I), wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein. The present invention relates to compounds inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.
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MODULATORS OF SOCE, COMPOSITIONS, AND USES THEREOF (Fri, 15 Dec 2017)
Compounds of Formula (I) able to modulate Store Operated Calcium Entry (SOCE). The disclosure also relates to the use of compounds of formula (I) for treatment of pathological conditions in which SOCE modulation might be beneficial, such as neglecting disorders linked to loss-or gain-of-function STIM1/Orai1 mutations, allergic disorders, pain, inflammatory diseases, autoimmune diseases or disorders, cancer and other proliferative diseases, neurodegenerative disorders, myelodysplastic syndromes, haematological diseases, cardiovascular diseases, degenerative diseases of the musculoskeletal system, liver diseases and disorders, kidney diseases, type I diabetes, graft rejection, graft-versus-host disease, allogeneic or xenogeneic transplantation, thyroiditis and viral infections.
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5-[3-[PIPERIDIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS 4 AND 5 INHIBITORS FOR TREATING E.G. OSTEOARTHRITIS (Fri, 15 Dec 2017)
The present invention discloses 5-[3-[piperazin-l-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives according to Formula (I), wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein. The present invention relates to compounds inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.
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N-(5S,6S,9R)-5-AMINO-6-(2,3-DIFLUOROPHENYL)-6,7,8,9-TETRAHYDRO-5H-CYCLOHEPTA[B]PYRIDIN-9-YL-4-(2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDIN-1-YL)PIPERIDINE-1-CARBOXYLATE SALT (Thu, 14 Dec 2017)
Disclosed is a hemisulfate salt of Compound (I): and crystalline forms of the hemisulfate salt. Also disclosed are methods of using the hemisulfate salt of Compound (1) as a CGRP receptor antagonist, and pharmaceutical compositions comprising the hemisulfate salt of Compound (I). The hemisulfate salt of Compound (I) is useful in treating, preventing, or ameliorating disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).
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SERINE/THREONINE KINASE INHIBITORS (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Compounds of Formula I or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="61.30mm" file="US20170348310A1-20171207-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROCYCLIC DERIVATIVES AS RORGAMMA MODULATORS (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The present invention provides novel compounds of formula (I) that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, fibrotic diseases, or cholestatic diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.59mm" wi="57.74mm" file="US20170349582A1-20171207-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED INDAZOLES UEFUL FOR TREATMENT AND PREVENTION OF ALLERGIC AND/OR INFLAMMATORY DISEASES IN ANIMALS (Fri, 08 Dec 2017)
The present application relates to the use of substituted indazoles for treatment and/or prophylaxis of allergic and/or inflammatory diseases in animals, especially for treatment and/or prophylaxis of atopic dermatitis, Flea Allergy Dermatitis, inflammatory bowel disease, osteoarthritis and inflammatory pain, non-infectious recurrent airway disease, insect hypersensitivity, asthma, respiratory disease, mastitis and endometritis in animals.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 01 Dec 2017)
Disclosed herein are inhibitors of IRAK protein kinase. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 01 Dec 2017)
Disclosed herein are inhibitors of IRAK protein kinase of formula (I). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 01 Dec 2017)
Disclosed herein are inhibitors of IRAK protein kinase of formula (I). Also disclosed are pharmaceutical compositions that include the compounds of formula (I). Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. Formula (I)
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JAK AND HDAC DUAL-INHIBITOR COMPOUNDS (Fri, 17 Nov 2017)
The present disclosure described provides novel dual inhibition compounds that specifically target the JAK-STAT and HDAC pathways, two distinct cellular pathways that are useful in the treatment of various diseases and disorders. In certain aspects, the compounds described herein are useful in the treatment of cellular proliferative and inflammatory diseases or disorders, such as graft vs. host disease. In particular embodiments, the compounds described herein inhibit JAK2 and HDAC6.
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USE OF RECOMBINANT LYMPHOCYTE ACTIVATION GENE-3 AS A COMPANION THERAPEUTIC FOR PATIENTS AT RISK FOR CARDIOVASCULAR DISEASE AND OTHER CHRONIC INFLAMMATORY DISEASES (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">A method for classifying patients at risk for cardiovascular disease, other chronic inflammatory diseases, cardiovascular and/or non-cardiovascular morbidity and mortality based on a risk assessment for lymphocyte activation gene 3 (LAG3) protein deficiency, and for mediating the risk using recombinant lymphocyte activation gene-3 or LAG3 mimetic as a companion therapeutic alone or in combination with a statin and/or an anti-hyperlipidemic drug. The risk assessment is two-prong, beginning with a qualitative determination whether a subject has or is predisposed to abnormal expression of inflammasomes, heightened risk for inflammation and/or to dysfunctional HDL, followed by a quantitative assay or genetic screen for a polymorphism that occurs in the coding sequence of the LAG3 gene. Given positive indication, recombinant LAG3 and/or LAG3 mimetic is used alone or in combination with the therapeutic use of a cholesterol mediating drug for treatment.</p>
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1-PYRAZOLYL-3-(4-((2-ANILINOPYRIMIDIN-4 -YL) OXY) NAPTHTHALEN-1 - YL) UREAS AS P38 MAP KNASE INHIBITORS (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">There are provided compounds of formula (I) which are inhibitors of the family of p38 mitogen-activated protein kinase enzymes, and to their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as asthma and COPD.</p>
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PYRIMIDINE COMPOUNDS AS JAK KINASE INHIBITORS (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">The invention provides compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.51mm" wi="55.20mm" file="US20170312280A1-20171102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of JAK kinases. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat gastrointestinal and other inflammatory diseases, and processes and intermediates useful for preparing such compounds.</p>
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ISOINDOLINE DERIVATIVE, INTERMEDIATE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">Provided are an isoindoline derivative, intermediate, preparation method, pharmaceutical composition and use thereof. The isoindoline derivative and the pharmaceutical composition thereof can regulate the production or activity of immunological cytokines, thus effectively treating cancer and inflammatory disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.68mm" wi="56.73mm" file="US20170313676A1-20171102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MODIFIED PIGMENT EPITHELIUM-DERIVED FACTOR (PEDF) PEPTIDES AND USES THEREOF FOR TREATING NEOVASCULAR DISEASES, INFLAMMATORY DISEASES, CANCER, AND FOR CYTOPROTECTION (Fri, 03 Nov 2017)
Disclosed are modified pigment epithelium-derived factor (PEDF) peptides, particulate carrier prodrugs thereof, and pharmaceutical compositions comprising the peptides or particulate carrier prodrugs. The peptides, particulate carrier prodrugs, and pharmaceutical compositions may be used to treat diseases and disorders that are amenable to treatment with anti-angiogenic agents, anti-tumorigenic agents, anti- fibrotic agents, chemotherapy-protecting agents, and immune stimulating agents.
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PYRIMIDINE COMPOUNDS AS JAK KINASE INHIBITORS (Fri, 03 Nov 2017)
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of JAK kinases. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat gastrointestinal and other inflammatory diseases, and processes and intermediates useful for preparing such compounds.
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ANALOGS OF YOHIMBINE AND USES THEREOF (Fri, 03 Nov 2017)
The present disclosure provides compounds of Formulae (I-A), (ΙI'), (III-A), (IV'), and (V-A), wherein the compounds are derived from or based on yohimbine. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, cancers, inflammatory diseases, autoimmune diseases, and infectious diseases) in a subject in need thereof. The present disclosure provides methods of preparing compounds of Formulae (I-A), (ΙI'), (III-A), (IV'), and (V-A). Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.
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A NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN-3,25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVER DISEASES AND ATHEROSCLEROSIS (Thu, 02 Nov 2017)
5-cholesten-3, 25-diol, disulfate (25HCDS) has been found to be an authentic PPAR ³ agonist and LXR antagonist, and is used for the therapy of lipid disorders and inflammatory diseases, including without limitation fatty liver, inflammatory bowel, and atherosclerotic diseases.
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Antagonistic DR3 Ligands (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to treatment of inflammatory diseases. In particular, the present invention relates to antagonistic DR3 ligands useful for treating inflammatory diseases.</p>
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HETEROBIFUNCTIONAL INHIBITORS OF E-SELECTINS AND CXCR4 CHEMOKINE RECEPTORS (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">Compounds, compositions, and methods for treatment and/or prevention of cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood are disclosed. For example, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described and pharmaceutical compositions comprising at least one of the same.</p>
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MODIFIED PIGMENT EPITHELIUM-DERIVED FACTOR (PEDF) PEPTIDES AND USES THEREOF FOR TREATING NEOVASCULAR DISEASES, INFLAMMATORY DISEASES, CANCER, AND FOR CYTOPROTECTION (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">Disclosed are modified pigment epithelium-derived factor (PEDF) peptides, particulate carrier prodrugs thereof, and pharmaceutical compositions comprising the peptides or particulate carrier prodrugs. The peptides, particulate carrier prodrugs, and pharmaceutical compositions may be used to treat diseases and disorders that are amenable to treatment with anti-angiogenic agents, anti-tumorigenic agents, anti-fibrotic agents, chemotherapy-protecting agents, and immune stimulating agents</p>
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BIOMARKERS AND METHODS FOR ASSESSING RESPONSE TO INFLAMMATORY DISEASE THERAPY (Fri, 27 Oct 2017)
Provided herein are methods for assessing response to inflammatory disease therapy. The methods include performing immunoassays to generate scores based on quantitative data for expression of biomarkers relating to inflammatory biomarkers to assess disease activity in inflammatory diseases, e.g., rheumatoid arthritis. Also provided are uses of inflammatory biomarkers for guiding treatment decisions.
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CONJUGATES COMPRISING RIPK2 INHIBITORS (Fri, 27 Oct 2017)
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.
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PHENYL UREA DERIVATIVES AS N-FORMYL PEPTIDE RECEPTOR MODULATORS (Fri, 20 Oct 2017)
The present invention relates to phenyl urea derivatives useful for the treatment of inflammatory diseases, pharmaceutical compositions containing them and their use as tools or as pharmaceuticals as modulators of the N-formyl peptide receptor (FPR), including FPR1 and FPR2, or as selective agonists of the FPR1 receptor.
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4-(AZETIDIN-1-YL)PYRIMIDINE DERIVATIVES WITH ANTI-MITOTIC AND ANTI-PROLIFERATIVE ACTIVITY (Fri, 20 Oct 2017)
The invention relates to 4-(azetidin-1-yl)pyrimidyl compounds of formula (I), wherein X and Y are, independently of each other CH or N; U is O, CHOH, CHCH2OH, C(CH3)OH, CO, CHNH2; R1 and R2 are, independently of each other H, F or CH3; and R3 is H or CH3; and related compounds with anti-mitotic and anti-proliferative properties, and methods of making use of such compounds in therapy or diagnostics to attenuate undesired cell proliferation, growth, migration, metastasis tumor formation, and inflammatory conditions. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious and inflammatory diseases using such compounds.
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BROMODOMAIN INHIBITORS (Fri, 20 Oct 2017)
The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, R6, X1, and X2 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising compounds of formula (I).
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4-(AZETIDIN-1-YL)PYRIMIDINE DERIVATIVES WITH ANTI-MITOTIC AND ANTI-PROLIFERATIVE ACTIVITY (Thu, 19 Oct 2017)
The invention relates to 4-(azetidin-1-yl)pyrimidyl compounds of formula (I), wherein X and Y are, independently of each other CH or N; U is O, CHOH, CHCH 2 OH, C(CH 3 )OH, CO, CHNH 2 ; R 1 and R 2 are, independently of each other H, F or CH 3 ; and R 3 is H or CH 3 ; and related compounds with anti-mitotic and anti-proliferative properties, and methods of making use of such compounds in therapy or diagnostics to attenuate undesired cell proliferation, growth, migration, metastasis tumor formation, and inflammatory conditions. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious and inflammatory diseases using such compounds.
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KINASE INHIBITORS (Fri, 13 Oct 2017)
<p id="p-0001" num="0000">There are provided compounds of formula I,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.40mm" wi="75.61mm" file="US20170291917A1-20171012-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein T, A, Q, Z, G, R<sup>4</sup>, R<sup>5a</sup>, R<sup>5b </sup>and n have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.</p>
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IL-17A/F HETEROLOGOUS POLYPEPTIDES AND THERAPEUTIC USES THEREOF (Fri, 13 Oct 2017)
<p id="p-0001" num="0000">The present invention is directed to a novel naturally occurring human cytokine that is comprised of a heterodimer of interleukin-17 and interleukin-17F designated herein as interleukin 17A/F (IL-17A/F). Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, specific antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.</p>
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SMALL MOLECULE REGULATORS OF STEROID RECEPTOR COACTIVATORS AND METHODS OF USE THEREOF (Fri, 13 Oct 2017)
Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.
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KINASE INHIBITORS (Fri, 13 Oct 2017)
There are provided compounds of formula I, (I) wherein T, A, Q, Z, G, R4, R5a, R5b and n have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
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CYCLIC UREA COMPOUNDS AS TROPOMYOSIN-RELATED KINASE (TRK) iNHIBITORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and/or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-receptor kinase B (TrkB), tropomyosin-receptor kinase C (TrkC), and/or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).</p>
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PHARMACEUTICAL COMPOSITIONS AND THEIR USE FOR TREATMENT OF CANCER AND AUTOIMMUNE DISEASES (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Described herein are combination therapies for cancer (such as lymphoid malignancies) and immune diseases (such as autoimmune diseases and inflammatory diseases). The therapies comprise the combined use of inhibitors of BTK, mTOR kinase, and Bcl-2 or their signaling pathways, and immunomodulatory drugs. Also described are pharmaceutical compositions and kits comprising these inhibitors.</p>
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Bruton's Tyrosine Kinase Inhibitors (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseeases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.78mm" wi="53.68mm" file="US20170283393A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHENYL UREA DERIVATIVES AS N-FORMYL PEPTIDE RECEPTOR MODULATORS (Fri, 06 Oct 2017)
The present disclosure relates to phenyl urea derivatives useful for the treatment of inflammatory diseases, pharmaceutical compositions containing them and their use as modulators of the N-formyl peptide receptor (FPR), including FPRl and FPR2, or as selective agonists of the FPRl receptor.
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BICYCLIC COMPOUND (Thu, 05 Oct 2017)
Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula: wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.
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MODULATORS OF THE RETINOID-RELATED ORPHAN RECEPTOR GAMMA (ROR-GAMMA) FOR USE IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES (Thu, 21 Sep 2017)
The present invention relates to retinoid-related orphan receptor gamma (ROR³) modulators of formula (I)v for use in the treatment of autoimmune or inflammatory diseases.
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NO- AND H2S- RELEASING COMPOUNDS (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">This disclosure relates to compounds containing both an NO-releasing moiety and an H<sub>2</sub>S-releasing moiety and the use of such compounds in treating inflammatory diseases, including cancers.</p>
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BICYCLIC UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF PAIN (Fri, 15 Sep 2017)
[0010131 Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
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Bromodomain inhibitors (Fri, 15 Sep 2017)
2 3 4 1 2 The present invention provides for compounds of formula (I) wherein A1 , A , A , A , X , X , Y L', G1 , R', and R1 have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF FIBROSIS (Sat, 09 Sep 2017)
The present invention discloses compounds according to Formula I, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6a, X, Cy1, Cy2, and the subscript n and m are as defined herein. The present invention relates to antagonists compounds of sphingosine 1-phosphate (SIP) receptor, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, inflammatory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering the compound of the invention.
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BIOMARKERS AND METHODS FOR PREDICTING RESPONSE TO DISCONTINUATION OF INFLAMMATORY DISEASE THERAPY (Sat, 09 Sep 2017)
Provided herein are methods for assessing response to inflammatory disease therapy. The methods include performing immunoassays to generate scores based on quantitative data for expression of biomarkers relating to inflammatory biomarkers to predict flare and sustained remission. The methods further include recommending discontinuation of a therapeutic regimen, or no change in a therapeutic regimen, based on the predictions generated by the quantitative data.
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KINASE INHIBITORS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">There are provided compounds of formulas III and VIIa:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="65.11mm" wi="75.61mm" file="US20170253563A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt or protected derivative thereof, wherein Z<sup>2 </sup>represents a structural fragment of formula V,</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="45.13mm" wi="69.85mm" file="US20170253563A1-20170907-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">wherein R<sup>1A </sup>to R<sup>1E</sup>, R<sup>2 </sup>to R<sup>4</sup>, R<sup>5a</sup>, L and X<sup>1 </sup>to X<sup>3 </sup>have meanings given in the description, which compounds have antiinflammatory activity, for example through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.</p>
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NOVEL IMIDAZOPYRIDAZINE COMPOUNDS AND THEIR USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">This disclosure provides novel imidazopyridazine compounds of formula (I) and pharmaceutical acceptable salt thereof, pharmaceutical compositions containing them, a process for preparing them, and their practical effect in inhibiting PI<sub>3</sub>K and potential use in treating a disease responsive to inhibition of PI<sub>3</sub>K, for example, an inflammatory disease, autoimmune disease or cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.67mm" wi="57.40mm" file="US20170253618A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHOD FOR PRODUCING INDOLE COMPOUND (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention aims to provide a new method for producing an indole compound or a salt thereof, which has an ITK inhibitory action, and is useful for the prophylaxis or treatment of inflammatory disease.</p> <p id="p-0002" num="0000">The present invention is a method for producing N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-(2S)-2-(morpholin-4-yl)propanamide, which comprises a step of reacting</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="85.17mm" wi="72.73mm" file="US20170253577A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof (Fri, 08 Sep 2017)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNKl a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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Urea derivatives and uses thereof (Fri, 08 Sep 2017)
The present invention provides novel compounds of any one of Formulae (I)-(II1), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration. glaucoma,. diabetic retinopathy, retinoblastoma, edema. uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof. Figure 1 2-theta (deg)
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ISOINDOLINE DERIVATIVE, INTERMEDIATE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF (Thu, 07 Sep 2017)
Provided are an isoindoline derivative, intermediate, preparation method, pharmaceutical composition and use thereof. The isoindoline derivative and the pharmaceutical composition thereof can regulate the production or activity of immunological cytokines, thus effectively treating cancer and inflammatory disease.
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METHODS OF DETECTING AND TREATING AIRWAY INFLAMMATORY DISEASES (Fri, 01 Sep 2017)
The present invention is related to novel methods for identifying and/or diagnosing and/or treating a population of subjects that are at risk for developing and/or have an inflammatory disease of the airways, including type 2 cytokine-driven airway inflammation.
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CONJUGATES OF PORPHYRINOID PHOTOSENSITIZERS AND GLYCEROL-BASED POLYMERS FOR PHOTODYNAMIC THERAPY (Thu, 31 Aug 2017)
Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. In addition, conjugates are provided in which these photosensitizers are attached to water-soluble polymers via cleavable linkers that can be cleaved in the body under specific conditions. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.
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6-ARYL-4-MORPHOLIN-1-YLPYRIDONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES (Fri, 25 Aug 2017)
The invention provides novel 6-aryl or 6-heteroaryl 4-morpholin-4-yl-pyhdine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R1, R2, R3 and R4 are as defined in the specification.
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6-HETEROCYCLYL-4-MORPHOLIN-4-YLPYRIDINE-2-ONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES (Fri, 25 Aug 2017)
The invention provides novel 6-heterocyclyl-4-morpholin-4-yl-pyridine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory disease, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R1, R2, R3 and A are as defined in the specification.
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METHODS AND COMPOSITIONS FOR T CELL GENERATION AND USES THEREOF (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Among the various aspects of the present disclosure is the provision of a method of treating an inflammatory bowel disease. Another aspect provides the provision of a screening method for therapeutic agents. Another aspect provides a method of detecting T<sub>reg </sub>cells to determine if a subject has an inflammatory disease. The present disclosure provides for methods of treatment, diagnosis, and screening for drugs for colitis and ileitis.</p>
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Fused pyrimidine derivatives for inhibition of tyrosine kinase activity (Wed, 16 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a novel fused pyrimidine derivative having an inhibitory activity for tyrosine kinases, and a pharmaceutical composition for preventing or treating cancers, tumors, inflammatory diseases, autoimmune diseases, or immunologically mediated diseases comprising same as an active ingredient.</p>
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Kinase inhibitors (Wed, 16 Aug 2017)
<p id="p-0001" num="0000">In compounds of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="51.31mm" wi="75.18mm" file="US09732063-20170815-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> R<sup>1 </sup>to R<sup>5</sup>, Ar and X<sup>1 </sup>to X<sup>3 </sup>have defined meanings. The compounds have anti-inflammatory activity (e.g., through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines. </p>
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TROPOMYOSIN-RELATED KINASE (TRK) INHIBITORS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and/or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-related kinase B (TrkB), tropomyosin-related kinase C (TrkC), and/or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).</p>
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NRF2 ACTIVATING COMPOUNDS AND USES THEREOF (Fri, 11 Aug 2017)
Aspects of the present disclosure include compounds that activate Nrf2. Such compounds find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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NRF2 ACTIVATING COMPOUNDS AND USES THEREOF (Fri, 11 Aug 2017)
Aspects of the present disclosure include compounds that activate Nrf2. Such compounds may find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Compound isolated from Pseudolysimachion rotundum var. subintegrum, the composition comprising the same for treating allergic disease, inflammatory disease, asthma or chronic obstructive pulmonary disease and the use thereof (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">A compound (3R,5S,5aS,6R,7S,8R,8aS)-8-chloro-8a-hydroxy-5-(2-hydroxy acetoxy) hexahydro-1H-3,6-methanocyclopenta[e][1,3]dioxepin-7-yl 3,4-dihydroxybenzoate (KS534), the isomer thereof, the pharmaceutically acceptable salt or solvates thereof, a composition comprising the same as an active ingredient for treating allergic disease, inflammatory disease, asthma or chronic obstructive pulmonary disease (COPD)</p>
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CCR9 ANTAGONIST COMPOUNDS (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Provided herein are compounds that inhibit CCR9 receptor function. Also provided herein are methods of treating inflammatory disease in a subject, comprising administering to the subject a compound of the invention. Accordingly, in one aspect, provided herein is a compound of Formula (1) or a pharmaceutically acceptable salt thereof. In another aspect, provided herein is a pharmaceutical composition, comprising a compound of Formula (1), and a pharmaceutically acceptable carrier.</p>
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Nrf2 activating compounds and uses thereof (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Aspects of the present disclosure include compounds that activate Nrf2. Such compounds find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.</p>
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Nrf2 activating compounds and uses thereof (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Aspects of the present disclosure include compounds that activate Nrf2. Such compounds may find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.</p>
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KINASE INHIBITORS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Compounds of formula I,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.12mm" wi="74.93mm" file="US20170209445A1-20170727-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">have anti-inflammatory activity. Exemplary mechanisms of action include inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases. The compounds have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.</p>
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METHODS AND SYSTEMS FOR PROCESSING PARTICLES (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Described herein are improved microfluidic devices and methods for processing cells that can improve cell quality, streamline workflows, and lower costs. Applications include research and clinical diagnostics in cancer, infectious disease, and inflammatory disease, among other disease areas.</p>
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IRAK4 INHIBITING AGENTS (Fri, 28 Jul 2017)
Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, and methods for their use and production. Formula (I) The compounds are IRAK-4 inhibitors useful for treating an inflammatory disease, an autoimmune disease, cancer, a cardiovascular disease, a disease of the central nervous system, a disease of the skin, an ophthalmic disease and condition, and a bone disease.
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QUINOLINE DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISEASES (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to a compound of formula (I) wherein: Formula (II) means an aromatic ring wherein V is C or N and when V is N; Q is N or O, provided that R″ does not exist when Q is O; R′ independently represent a hydrogen atom or a group chosen among a (C<sub>1</sub>-C<sub>3</sub>)alkyl group, a halogen atom, a hydroxy! group, a —COOR<sub>1 </sub>group, a —NO2 group, a —NR<sub>1</sub>R<sub>2 </sub>group, a morpholinyl or a morpholino group, a N-methylpiperazinyl group, a (C<sub>1</sub>-C3)fluoroalkyl group, a —O—P(=O)—(OR<sub>3</sub>XOR<sub>4</sub>) group, a (C<sub>1</sub>-C<sub>4</sub>)alkoxy group and a —CN group, and can further be a group chosen among: (IIa), (IIIa) or anyone of its pharmaceutically acceptable salt, for use in the treatment and/or prevention of an inflammatory disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="98.13mm" wi="65.28mm" file="US20170204063A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF HISTONE DEACETYLASE (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula (I), (II), (IIa), (III), (IV), (V), or (VI)) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.</p>
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QUINAZOLIN-4 (3H)-ONE DERIVATIVES USED AS P13 KINASE INHIBITORS (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to the compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="68.41mm" wi="61.04mm" file="US20170202841A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and to compositions comprising the same and to the use of the compound and to compositions of the compound in treatment, for example in the treatment of inflammatory diseases, in particular respiratory inflammatory disease. The invention also extends to methods of making the said compound.</p>
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COMPOUNDS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds and pharmaceutical compositions thereof which may be useful in the treatment and/or prevention of various conditions. The present invention also provides methods of preparing such compounds and compositions, and methods of using the same.</p>
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CRYSTAL FORMS OF IMMUNOMODULATORY DRUG POMALIDOMIDE AND CO-CRYSTAL WITH GENTISIC ACID (Fri, 21 Jul 2017)
The present invention relates to novel solid crystal forms of Pomalidomide named Form B, Form M, Pomalidomide: Gentisic acid co-crystal and their preparation. Advantageously, these solid forms are used in pharmaceutical compositions for the treatment and the prevention of multiple myeloma, of inflammatory diseases, of autoimmune diseases, of immune diseases, of myelodysplastic syndrome, of myeloproliferative disorders, of anemia, of scleroderma, amyloidosis or of other diseases associated with unwanted angiogenesis.
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APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.98mm" wi="66.80mm" file="US20170196844A1-20170713-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, X<sup>5</sup>, X<sup>6</sup>, X<sup>7</sup>, X<sup>8</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).</p>
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A QUINOLINE DERIVATIVE FOR THE TREATMENT OF INFLAMMATORY DISEASES AND AIDS (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to a compound of formula (1) in the form of a base or addition salt with an acid, particularly a pharmaceutically acceptable acid. It further relates to a pharmaceutical composition including the compound and at least one pharmaceutically acceptable excipient, to a process for preparing said compound and to a corresponding intermediate compound.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.77mm" wi="73.32mm" file="US20170197938A1-20170713-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Heterocyclic GSK-3 allosteric modulators (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to heterocyclic substituted quinoline derivatives as allosteric inhibitors of the glycogen synthase kinase-3 (GSK-3) enzyme. Therefore, these compounds are useful for the manufacturing of a medicament designed for the treatment and/or prevention of diseases wherein GSK-3 is involved, such as neurodegenerative diseases, inflammatory diseases, cancer, diabetes, and to promote various regenerative processes.</p>
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Method of providing monoclonal auto-antibodies with desired specificity (Fri, 14 Jul 2017)
Provided are novel binding molecules of human origin, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize antigens such as native endogenous proteins associated with, e.g., immune response, autoimmune disorders, inflammatory diseases, metabolic disorders, vascular function, neurodegenerative diseases or tumors. More particularly, a human Auto-Immunosome and corresponding monoclonal antibody reservoir are provided. In addition, pharmaceutical compositions, kits and methods for use in diagnosis and therapy of are described.
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ANTIBODIES THAT BIND AND BLOCK TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-1 (TREM-1) (Fri, 07 Jul 2017)
<p id="p-0001" num="0000">The invention relates to antibodies that are capable of specifically binding TREM-1 and preventing the activation of TREM-1, a protein expressed on monocytes, macrophages and neutrophils. Such antibodies find utility in the treatment of individuals with an inflammatory disease, such as rheumatoid arthritis and inflammatory bowel disease.</p>
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MULTICYCLIC COMPOUNDS AND USES THEREOF (Fri, 07 Jul 2017)
The present invention relates to multicyclic compounds containing a urea or a guanidine moiety, or pharmaceutically acceptable salts or compositions thereof represented by Structural Formula (IA) or a pharmaceutically acceptable salt thereof and pharmaceutical comopositions comprising the multicyclic compounds. The invention also relates to a method for treating a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T-Cell mediated autoimmune disesase) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.
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COMBINATION THERAPIES FOR HEMATOLOGIC MALIGNANCIES (Thu, 06 Jul 2017)
The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administration of a compound of formula A, wherein R is H, halo, or C1-C6 alkyl; R' is C1-C6 alkyl; or a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable excipient; and one or more additional therapeutic agents optionally selected from the group consisting of bendamustine, rituximab, and ofatumumab.
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HETEROCYCLIC COMPOUND (Thu, 06 Jul 2017)
The present invention provides a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of autoimmune diseases and/or inflammatory diseases, graft versus host disease, cancers, central nervous diseases including neurodegenerative diseases and the like, and a medicament comprising the compound. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
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COMPOSICIONES DE CICLODEXTRINA Y DERIVADOS DE BUDESONIDA Y METODOS. (Wed, 05 Jul 2017)
The present invention relates to novel and useful pharmaceutical compositions formulated with a cyclodextrin compound and a budesonide derivative for the treatment and/or prevention of pulmonary inflammatory disease. The present invention also relates to a novel and useful analytical technique for the detection and the quantification of HP-ß-CD in solution. More specifically, the present invention relates to the use of a validated 1H NMR analysis for the detection and quantification of cyclodextrins directly in pharmaceutical formulations without any extraction or separation steps for liquid formulations.
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INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.51mm" wi="75.10mm" file="US20170183327A1-20170629-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7) (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="61.98mm" wi="69.85mm" file="US20170183355A1-20170629-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL SESQUITERPENE DERIVATIVES AND THEIR USE IN INFLAMMATION OR CANCER TREATMENT (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">A new class of sesquiterpene derivative useful for treating cancerous and inflammatory diseases are disclosed. These deoxyelephantopin derivatives are effective in suppressing proliferation, migration, mobility, invasion, growth, and/or metastasis of cancer cells in a patient, or useful for enhancing an anti-proliferative effect of another anti-cancer drug on cancer cells when treating a patient, or for sensitizing and/or enhancing an anti-cancer effect of a gluthathione synthesis blocker on inhibition of triple negative breast cancer cell activity, or for treatment and/or prophylaxis of lipopolysaccharide-stimulated inflammatory response in a patient, or for all of the above. Also disclosed are methods of preparing the deoxyelephantopin derivatives.</p>
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METHOD FOR PRODUCING MONOMETHYL FUMARATE COMPOUNDS (Fri, 30 Jun 2017)
The present invention relates to a novel method for preparing monomethyl fumarate, which can preferably be used in the treatment and/or prevention of systemic diseases, autoimmune diseases, inflammatory diseases such as multiple sclerosis and psoriasis. Further, the present invention relates to the use of specific compounds as intermediates in the process for preparing a monomethyl fumarate prodrug.
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IMMUNE CELL-TARGETED PARTICLES (Fri, 30 Jun 2017)
The present disclosure provides particles with a polymeric core containing a pharmaceutically active agent; and an antibody fragment conjugated to the surface of the particle, wherein the antibody fragment targets an endogenous immune cell subset (e.g., an endogenous T-cell or a myeloid-derived suppressor cell). The present invention provides methods for forming and methods for using the particles. The particles described herein may be useful in treating and/or preventing proliferative disease, inflammatory disease, or neoplastic disorders (e.g., cancer, autoimmune diseases). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a particle described herein.
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COMPOUNDS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASE (Fri, 30 Jun 2017)
Provided herein are compounds that inhibit the phosphorylation of MAPK and thus are compositions and methods for treating cancer and inflammatory disease.
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GLYCOSYLATED INDOLOCARBAZOLES, METHOD FOR OBTAINING SAME AND USES THEREOF (Thu, 29 Jun 2017)
Glycosylated indolocarbazoles of formula (II), method for obtaining same and uses thereof. This invention relates to rebeccamycin and staurosporine derivatives obtained by fermentation of recombinant bacterial strains. The invention also relates to the methods used to obtain the recombinant strains and the production of rebeccamycin and staurosporine derivatives. The invention also relates to bacterial strains that are of use for the production of rebeccamycin and staurosporine derivatives. Lastly, the rebeccamycin and staurosporine derivatives described herein are applicable to the field of human health, specifically for manufacturing drugs that are of use in the treatment of tumour, neurological and inflammatory diseases.
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2-phenylbenzofuran derivatives, method for preparing the same and use of the same for treating inflammatory disease (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to a novel 2-phenylbenzofuran derivative or a pharmaceutically acceptable salt thereof, a production method for the same, and a pharmaceutical composition for preventing or treating an inflammatory disease comprising the same as an active ingredient, and the novel 2-phenylbenzofuran derivative or the pharmaceutically acceptable salt thereof according to the present invention is outstandingly effective in suppressing NO, IL-6, and TNF-alpha induced by macrophages, and therefore can advantageously be used in a pharmaceutical composition for preventing or treating an inflammatory disease.</p>
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COMPOUNDS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASE (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Provided herein are compounds that inhibit the phosphorylation of MAPK and thus are useful in compositions and methods for treating cancer and inflammatory disease.</p>
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INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7) (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides novel compounds described herein, such as of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="11.35mm" wi="54.78mm" file="US20170174692A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.19mm" wi="73.58mm" file="US20170173031A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.</p>
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METHODS FOR IDENTIFYING INHIBITORS OF "STIMULATOR OF INTERFERON GENE"-DEPENDENT INTERFERON PRODUCTION (Fri, 23 Jun 2017)
The present invention relates to the use cyclic-di-nucleotide and related scaffold molecules that measurably inhibit STING signaling, and methods for their use in identifying more potent inhibitors of STING signaling. In particular, the methods provided can be used to identify potent inhibitors of STING signaling, which are useful in the treatment of autoimmune and inflammatory diseases. Also provided are compounds having STING inhibitory activity useful in the treatment of autoimmune and inflammatory diseases.
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SMALL MOLECULES FOR INHIBITING CHEMOKINE ACTIVITY, A KINASE ACTIVITY AND/OR CANCER CELLS GROWTH (Fri, 23 Jun 2017)
Compounds capable of, or usable in, inducing death of cancer cells and/or modulating a biological activity of a chemokine e.g., cell migration, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or inhibiting a kinase and/or in treating a disease or disorder associated with an activity of a kinase, such as cancer and inflammatory diseases and disorders, are provided herein. The compounds are collectively represented by Formulae (Ia) or (Ib): wherein A, B D, E, G and R1-R5 are as defined in the specification.
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SMALL MOLECULES AGAINST CANCER (Fri, 23 Jun 2017)
Compounds capable of, or usable in, killing cancer cells, and/or modulating a biological activity of a chemokine, and/or inhibiting a kinase, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or treating disease and disorders such as cancer and inflammatory diseases and disorders, are provided herein. The compounds are listed in Tables 2, 4 and 5, and/or are represented by Formulae I, IV, V and VI, as defined in the specification. Methods utilizing these compounds are also provided.
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HETEROARYL AMIDE SULTAM DERIVATIVES AS RORc MODULATORS (Fri, 23 Jun 2017)
Compounds of the formula I: (I) or a pharmaceutical salt thereof, wherein m, n, p, q, Het, A, W, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
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IL-17A/F HETERODIMERIC POLYPEPTIDES AND THERAPEUTIC THEREOF (Thu, 22 Jun 2017)
The present invention is directed to a novel naturally occurring human cytokine that is comprised of a heterodimer of interleukin-17 and interleukin-17F designated herein as interleukin 17A/F (IL-17 A/F). Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, specific antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.
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CARBAZOLE COMPOUNDS AND THERAPEUTIC USES OF THE COMPOUNDS (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">Compounds of the general structural formula (I) and (II) and use of the compounds and salts and hydrates thereof, as therapeutic agents are disclosed. Treatable diseases and conditions include cancers, inflammatory diseases and conditions, and immunodeficiency diseases. (I), (II).</p>
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Biomarkers and Methods for Measuring and Monitoring Inflammatory Disease Activity (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">Biomarkers useful for diagnosing and assessing inflammatory disease are provided, along with kits for measuring their expression. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples. The biomarkers include at least two biomarkers selected from the DAIMRK group and the score is a disease activity index (DAI).</p>
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O-GLCNAC TRANSFERASE (OGT) INHIBITORS AND USES THEREOF (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">The present invention provides inhibitors of O-GlcNAc transferase. Typically, the inhibitors are quinolinone-6-sulfonamides. The invention also provides pharmaceutical compositions thereof and methods for using the same in diabetes and complications thereof, metabolic diseases, neurodegenerative diseases, proliferative diseases (e.g., cancers), autoimmune diseases, and inflammatory diseases.</p>
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2-AMINO-BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS 5-LIPOXYGENASE AND/OR PROSTAGLANDIN E SYNTHASE INHIBITORS (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X<sup>1 </sup>and X<sup>2 </sup>are independently, at each occurrence, CR<sup>5 </sup>or N; Y is C<sub>1</sub>-C<sub>6 </sub>alkylene, wherein alkylene is optionally substituted with one to two C<sub>1</sub>-C<sub>3 </sub>alkyl groups; R<sup>1 </sup>is selected from the group consisting of hydrogen, halogen, C<sub>1</sub>-C<sub>6 </sub>alkoxy, —NH<sub>2</sub>, —NHR<sup>6</sup>, —NR<sup>7</sup>R<sup>8 </sup>and —NH—(R<sup>9</sup>)<sub>n</sub>—R<sup>10</sup>, n being 0 or 1; R<sup>2 </sup>is selected from the group consisting of hydrogen, halogen, C<sub>1</sub>-C<sub>6 </sub>alkyl, —NH<sub>2</sub>, —NHR<sup>6</sup>, —NR<sup>7</sup>R<sup>8 </sup>and —NH—(R<sup>9</sup>)<sub>n</sub>—R<sup>10</sup>; R<sup>3 </sup>is selected from the group consisting of hydrogen, hydroxyl, OR<sup>11</sup>, —NR<sup>7</sup>R<sup>8</sup>, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>3</sub>- C<sub>10 </sub>cycloalkyl, C<sub>1</sub>-C<sub>3 </sub>haloalkyl, —C(O)NHR<sup>11</sup>, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R<sup>a </sup>groups; and R<sup>4 </sup>is selected from the group consisting of —NH<sub>2</sub>, —N(R<sup>12</sup>)(V)<sub>p</sub>R<sup>13</sup>, —NH(V)<sub>p</sub>—OR<sup>14</sup>, —NHC(O)R<sup>15</sup>, and groups of formula 1a shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="62.48mm" wi="66.89mm" file="US20170166563A1-20170615-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals (Fri, 16 Jun 2017)
3-Heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals The present invention relates to compounds of the formula I, wherein Ht, G, R10, R30 , R40 , R50 and R60 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.
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GADD45BETA TARGETING AGENTS (Thu, 15 Jun 2017)
Compounds based around tetrapeptide, tripeptide and dipeptide moeties and corresponding peptiod moeties. Related methods and pharmaceutical compositions for use in treatment of cancer, inflammatory diseases, and other disorders.
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3-(5-SUBSTITUTED-4-OXOQUINAZOLIN-3(4H)-YL)-3-DEUTERO-PIPERIDINE-2,6-DIONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">The invention provides 3-deuterium-enriched 3-(5-substituted-4-oxoquinazolin-3(4H)-yl)-piperidine-2,6-diones, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same, such as in the treatment of cancer, an immune-related disease, or an inflammatory disease.</p>
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BINDING INHIBITOR BETWEEN TCTP DIMER TYPE IGE-DEPENDENT HISTAMINE RELEASING FACTOR AND RECEPTOR THEREOF, AND USE THEREOF (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to a receptor-binding domain of an IgE-dependent histamine releasing factor (HRF), and a use thereof, and more specifically, ascertains, as an HRF structual region, and a FL domain and an H2 domain which bind to a receptor of HRF existing in a cell membrane, ascertains the C-terminus domain of the HRF, and ascertains that a material binding thereto inhibits IL-8 secretion, thereby determining that the FL and H2 domains and the C-terminus domain can be utilized in: the development of a therapeutic agent for treatment and prevention of HRF-related disease including allergic diseases such as asthma, bronchitis, chronic obstructive pulmonary disease, bronchiectasis, rhinitis, atopic dermatitis, hives (urticaria), hay fever, conjunctivitis, and anaphylaxis; inflammatory diseases such as bronchitis, pneumonia, arthritis, nephritis, psoriasis, dermatitis, Crohn's disease, enteritis, gingivitis, arteriosclerosis, coronary arteritis, hepatitis, Behcet's disease, bladder cancer, prostatitis, pyelonephritis, glomerulonephritis, osteomyelitis, thyroiditis, uveitis, abdominal cavity inflammation, meningitis, pulmonary fibrosis and rheumatoid arthritis; and malaria, and a method for screening for the HRF-related diseases.</p>
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PROCESSES FOR THE PREPARATION OF (R)-2-(7-(4-CYCLOPENTYL-3-(TRIFLUOROMETHYL)BENZYLOXY)-1,2,3,4-TETRAHYDROCYCLOPENTA[B]INDOL-3-YL)ACETIC ACID AND SALTS THEREOF (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to processes and intermediates useful in the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia) and salts thereof, an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development and atherosclerosis).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.49mm" wi="75.69mm" file="US20170159088A1-20170608-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Alpha-7 nicotinic acetylcholine receptor modulators and uses thereof-I (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to chemical compounds of formula (I), with the substituents as described in the specification, useful in the positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR). The invention also relates to the use of these compounds in the treatment or prevention of a broad range of diseases in which the positive modulation of α7 nAChR is advantageous, including neurodegenerative and neuropsychiatric diseases and also neuropathic pain and inflammatory diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.90mm" wi="29.04mm" file="US09790173-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">Compounds of formula (I), defined herein, act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for the prevention and/or treatment of broncho-obstructive or inflammatory diseases.</p>
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ANTI-GITR ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides antagonist antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., reduce, deactivate, or inhibit GITR activity. The present disclosure also provides methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human GITR and modulates GITR activity, e.g., reduces, deactivates, or inhibits GITR activity.
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ANTI-OX40 ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.
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LIPID COMPOUNDS AND COMPOSITIONS AND THEIR OPTHALMIC USE (Fri, 09 Jun 2017)
The invention relates to lipid compounds of formula (I) and their pharmaceutically acceptable salts for the prevention and/or treatment of ophthalmic disorders such as retinal degenerative disorders and ocular inflammatory diseases: (I) (wherein R1 is either a C9 to C22 alkyl group, or a C9 to C22 alkenyl group having from 1 to 6 double bonds; R2 is selected from the group consisting of a halogen atom, a hydroxy group, an alkyl group, an alkoxy group, an alkylthio group, a carboxy group, an acyl group, an amino group, and an alkylamino group; R3 is a hydrogen atom, or a group R2; R4 is a carboxylic acid or a derivative thereof; and X is methylene (-CH2-), or an oxygen or sulfur atom).
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ANTI-GITR ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides antibodies that specifically bind to human GITR, as well as compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and deactivate, reduce, or inhibit GITR activity. The present disclosure also provides methods for treating autoimmune or inflammatory diseases disorders, by administering an antibody that specifically binds to human GITR and deactivates, reduces, or inhibits GITR activity.
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ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides multispecific (e.g., bispecific) antibodies that specifically bind to human GITR and/or human OX40 as well as compositions comprising such antibodies. In a specific aspect, the multispecific antibodies specifically bind to human GITR and OX40 and modulate GITR and/or OX40 activity, e.g., enhance, activate, or induce GITR and/or OX40 activity, or reduce, deactivate, or inhibit GITR and/or OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., enhances, activates, or induces GITR and/or OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., reduces, deactivates, or inhibits GITR and/or OX40 activity.
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HOMOBISPIPERIDINYL DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 09 Jun 2017)
In its many embodiments, the present invention provides certain substituted bispiperidinyl compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein ring A, ring B, R1, R2, R3, L, R4, X, Z, Li, Q and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver Χ-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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ANTI-OX40 ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or diminish, deactivate, or suppress OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., diminishes, deactivates, or suppresses OX40 activity.
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PHARMACEUTICAL FORMULATIONS (Fri, 02 Jun 2017)
Disclosed herein is glutathione in conjunction with an isoselenazol or isothiazol derivative, e.g., ebselen or ebsulfur derivative, to treat diabetes, lupus, or other chronic inflammatory disease. The glutathione is preferably provided in a rapid release oral formulation that presents the glutathione for absorption in the first part of the ileum. The isoselenazol or isothiazol derivative is preferably provided in a delayed release formulation to avoid overlapping high enteric concentration. These may be provided within the same unit dosage form.
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Methods of Treating Cancers, Immune and Autoimmune Diseases, and Inflammatory Diseases Based on BTK Occupancy and BTK Resynthesis Rate (Fri, 26 May 2017)
<p id="p-0001" num="0000">In an embodiment, therapeutic methods and uses of Bruton's Tyrosine Kinase (BTK) inhibitors for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.</p>
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BENZIMIDAZOLE DERIVATIVES AS PI3 KINASE INHIBITORS (Thu, 25 May 2017)
The invention relates to benzimidazole derivatives of formula (I) which modulate, notably inhibit the activity or function of the phosphoinositide 3'-OH kinase family (PI3 kinases), suitably PI3K±, PI3K´, PI3K² and/or PI3K³. The invention further relates to these benzimidazoles for use in the treatment of disease states selected from autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. Especially, the invention relates to PI3K² selective benzimidazoles for use in treating cancer.
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ARYL SULTAM DERIVATIVES AS RORc MODULATORS (Fri, 19 May 2017)
<p id="p-0001" num="0000">Compounds of the formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.44mm" wi="69.85mm" file="US20170137393A1-20170518-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4</sup>, Y, Z, A, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, R<sup>9</sup>, R<sup>10</sup>, R<sup>11</sup>, R<sup>12 </sup>and R<sup>13 </sup>are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis, muscular sclerosis and psoriasis.</p>
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THERAPEUTIC/ PREVENTIVE AGENT CONTAINING COUMARIN DERIVATIVE AS ACTIVE INGREDIENT (Fri, 19 May 2017)
<p id="p-0001" num="0000">A method for prophylactically or therapeutically treating an inflammatory disease and/or degenerative intervertebral disk disease in a subject is disclosed. The method includes administering to the subject an effective amount of a coumarin derivative represented by formula (I), or a pharmaceutically acceptable salt or hydrate thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.60mm" wi="60.54mm" file="US20170135985A1-20170518-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Each of R1 and R2 is independently (a) phenyl optionally substituted with alkoxy, alkyl, cyano, nitro, hydroxy, trifluoromethyl, amino, carboxy, alkoxycarbonyl, phenyl, or one or two halogen(s), (b) pyridyl, (c) alkyl, or (d) thienyl.</p>
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CYANOPYRIDINE DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 19 May 2017)
In its many embodiments, the present invention provides substituted cyanopyridine containing compounds of the Formula (I): and acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, Q, and the moiety are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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BISPIPERIDINYL DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 19 May 2017)
In its many embodiments, the present invention provides certain substituted bispiperidinyl compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, Q and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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SUBSTITUTED PYRAZOLOPYRIDINAMINES (Fri, 19 May 2017)
The present invention relates to substituted pyrazolopyridinamine compounds of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyperproliferative, angiogenesis disorders, inflammatory diseases or diseases associated with inflammatory pain, as a sole agent or in combination with other active ingredients.
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Urea derivatives and uses thereof (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention provides novel compounds of any one of Formulae (I)-(III), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="111.17mm" wi="64.01mm" file="US09802922-20171031-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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4-alkynyl imidazole derivative and medicine comprising same as active ingredient (Fri, 12 May 2017)
<p id="p-0001" num="0000">There are provided 4-alkynylimidazole derivatives represented by the following general formula (I) or pharmaceutically acceptable salts thereof; the derivatives have a superior EP4 receptor antagonistic action and are useful as pharmaceuticals for the treatment of diseases associated with the EP4 receptor, for example, as anti-inflammatory and/or analgesic drugs for inflammatory diseases and diseases that involve various kinds of pains, and further as pharmaceuticals for the treatment of immune diseases that result from inflammations as evoked by tissue destruction due to the activation of Th1 cells and/or Th17 cells:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="53.42mm" wi="69.85mm" file="US09855257-20180102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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4,5,6,7-TETRAHYDRO-1H-IMIDAZO[4,5-C]PYRIDINE AND 1,4,5,6,7,8-HEXAHYDROIMIDAZO[4,5-D]AZEPINE DERIVATIVES AS JANUS KINASE INHIBITORS (Fri, 12 May 2017)
There are provided compounds of formula I, wherein X, Ak, s, A, R1 and R2 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of the JAK family) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
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4,5,6,7-TETRAHYDRO-1H-IMIDAZO[4,5-C]PYRIDINE AND 1,4,5,6,7,8-HEXAHYDROIMIDAZO[4,5-D]AZEPINE DERIVATIVES AS JANUS KINASE INHIBITORS (Fri, 12 May 2017)
There are provided compounds of formula (I), wherein X, Ak, s, L, Q, R1 and R2 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of the JAK family) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
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METHOD FOR PRODUCING INDOLE COMPOUND (Thu, 11 May 2017)
The present invention aims to provide a new method for producing an indole compound or a salt thereof, which has an ITK inhibitory action, and is useful for the prophylaxis or treatment of inflammatory disease. The present invention is a method for producing N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-(2S)-2-(morpholin-4-yl)propanamide, which comprises a step of reacting with
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BIOLOGICALLY ACTIVE OLIGONUCLEOTIDES CAPABLE OF MODULATING THE IMMUNE SYSTEM (Thu, 11 May 2017)
The present invention relates to methods of identifying oligonucleotides capable of modulating the immune system in a mammalian subject, comprising analysis of which tertiary structural type said oligonucleotide adopts, in phosphate-buffered saline solution. Further, the invention provides oligonucleotides identifiable by the methods of the invention and to their use in methods of treating diseases, such as inflammatory diseases, autoimmune diseases, infectious diseases, neurodegenerative diseases and cancer.
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COMBINATION THERAPIES FOR HEMATOLOGIC MALIGNANCIES (Fri, 05 May 2017)
<p id="p-0001" num="0000">The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administration of a compound of formula A,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="46.23mm" wi="62.06mm" file="US20170119771A1-20170504-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein R is H, halo, or C1-C6 alkyl; R′ is C1-C6 alkyl; or</li> <li id="ul0002-0002" num="0000">a pharmaceutically acceptable salt thereof; and</li> <li id="ul0002-0003" num="0000">optionally a pharmaceutically acceptable excipient; and</li> <li id="ul0002-0004" num="0000">one or more additional therapeutic agents optionally selected from the group consisting of bendamustine, rituximah, and ofatumumab.</li> </ul> </li> </ul> </p>
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COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY (Fri, 05 May 2017)
<p id="p-0001" num="0000">Compounds of formula I, defined herein, act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for treating broncho-obstructive and inflammatory diseases.</p>
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DENDRIMER COMPOSITIONS AND USE IN TREATMENT OF NECROTIZING ENTEROCOLITIS AND OTHER GASTROINTESTINAL DISORDERS (Fri, 05 May 2017)
<p id="p-0001" num="0000">A dendrimer formulation, such as a PAMAM dendrimer or a multiarm PEG polymeric formulation has been developed for oral administration to the gastrointestinal tract for treatment of inflammatory diseases associated with infection or cancer. In the preferred embodiment, the dendrimers are in the form of dendrimer nanoparticles comprising poly(amidoamine) (PAMAM) hydroxyl-terminated dendrimers covalently linked to at least one therapeutic, prophylactic or diagnostic agent for treatment of one or more symptoms of necrotizing enterocolitis.</p>
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BET-PROTEIN INHIBITING 3,4-DIHYDROPYRIDO[2,3-B]PYRAZINONES WITH META-SUBSTITUTED AROMATIC AMINO- OR ETHER GROUPS (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to BET protein-inhibitory, especially BRD4-inhibitory 3,4-dihydropyrido[2,3-b]pyrazinones with a meta-substituted aromatic amino or ether group of the general formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.03mm" wi="62.57mm" file="US20170121322A1-20170504-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which A, X, Y, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6 </sup>and n are each as defined in the description, to pharmaceutical compositions comprising the compounds according to the invention, and to the prophylactic and therapeutic use thereof in the case of hyperproliferative disorders, especially in the case of tumour disorders.</p> <p id="p-0004" num="0000">Furthermore, this invention relates to the use of BET protein inhibitors in viral infections, in neurodegenerative disorders, in inflammatory diseases, in atherosclerotic disorders and in male fertility control.</p>
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Lanthionine synthetase C-like 2-based therapeutics (Fri, 05 May 2017)
<p id="p-0001" num="0000">Provided are compounds that target the lanthionine synthetase C-like protein 2 pathway. The compounds can be used to treat a number of conditions, including infectious disease, autoimmune disease, diabetes, and a chronic inflammatory disease.</p>
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DENDERIMER COMPOSITIONS AND USE IN TREATMENT OF NECROTIZING ENTEROCOLITIS AND OTHER GASTROINTESTINAL DISORDERS (Fri, 05 May 2017)
A dendrimer formulation, such as a PAMAM dendrimer or a multiarm PEG polymeric formulation has been developed for oral administration to the gastrointestinal tract for treatment of inflammatory diseases associated with infection or cancer. In the preferred embodiment, the dendrimers are in the form of dendrimer nanoparticles comprising poly(amidoamine) (PAMAM) hydroxyl-terminated dendrimers covalently linked to at least one therapeutic, prophylactic or diagnostic agent for treatment of one or more symptoms of necrotizing enterocolitis.
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Diaryl urea derivatives as p38 kinase inhibitors (Fri, 05 May 2017)
There are provided compounds of formula I, wherein R<sp>1A</sp> to R<sp>1E</sp>, R<sp>2</sp> to R<sp>4</sp>, R<sp>5a</sp>, L and X1 to X3 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
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4-(4-(4-phenylureido-naphthalen-1-yl)oxy-pyridin-2-yl)amino-benzoic acid derivative as p38 kinase inhibitor (Fri, 05 May 2017)
There is provided a compound of formula I, which compound has antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and has use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
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Benzimidazole derivatives as PI3 kinase inhibitors (Fri, 28 Apr 2017)
<p id="p-0001" num="0000">This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.</p>
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NEW DERIVATIVES OF LICOFELONE (Fri, 28 Apr 2017)
The present invention relates to novel derivatives, preferably prodrugs, of licofelone suitable as a medicament, preferably in the treatment and/or prevention of systemic diseases, autoimmune diseases or inflammatory diseases. Further, the invention relates to a pharmaceutical composition comprising the novel compounds. The compounds are of formula (I) where L is a linear organic residue comprising 2 to 30 carbon atoms, and R is -OH or -OOCR', wherein -OOCR' is a carboxylate group which is hydrolyzable during small intestinal transit. Formula (I)
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6-[5-AMINO-6-(2-ETHOXYETHOXY)-IMIDAZO[4,5-B]PYRIDIN-3-YL]-NICOTINONITRILE DERIVATIVES AND THEIR USE AS IRAK INHIBITORS (Fri, 28 Apr 2017)
The present invention discloses compounds according to Formula (I): wherein R1, R2, and Cy are as defined herein. The present invention relates to compounds inhibiting IRAK family kinases, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of inflammatory diseases, autoimmune diseases and/or proliferative diseases by administering the compound of the invention.
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DERIVATIVES OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (Fri, 28 Apr 2017)
The present invention relates to novel compounds, e.g. for use as a medicament. In particular, the present invention relates to novel derivatives of certain nonsteroidal anti-inflammatory drugs, suitable as a medicament, preferably in the treatment and/or prevention of systemic diseases, autoimmune diseases, and/or inflammatory diseases, for example osteoarthritis, rheumatoid arthritis, multiple sclerosis and psoriasis. Further, the invention relates to a pharmaceutical composition comprising the novel compounds.
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Small Molecule Transcription Modulators of Bromodomains (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">This disclosure relates generally to compounds and compositions comprising one or more indole analogs. These compounds are useful for treating diseases associated with NF-kB and p53 activity, such as cancer and inflammatory diseases.</p>
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CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS AS PIN1 MODULATORS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
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CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS AS PIN1 MODULATORS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
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CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS (Fri, 21 Apr 2017)
Formula (I); Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
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CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
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BINDING INHIBITOR BETWEEN TCTP DIMER TYPE IGE-DEPENDENT HISTAMINE RELEASING FACTOR AND RECEPTOR THEREOF, AND USE THEREOF (Thu, 20 Apr 2017)
The present invention relates to a receptor-binding domain of an IgE-dependent histamine releasing factor (HRF), and a use thereof and, more specifically, ascertains, as an HRF framework region, an FL domain and an H2 domain which bind to a receptor of an HRF existing in a cell membrane, ascertains the C-terminus of the HRF, and ascertains that a material binding thereto inhibits IL-8 secretion, thereby determining that the FL and H2 domains and the C-terminus can be utilized in: the development of a therapeutic agent for and prevention of HRF-related diseases including malaria and inflammatory diseases such as asthma, bronchitis, chronic obstructive pulmonary disease, bronchiectasis, rhinitis, atopic dermatitis, hives, hay fever, conjunctivitis, anaphylactic allergic diseases, pneumonia, arthritis, nephritis, psoriasis, dermatitis, Crohn's disease, enteritis, gingivitis, arteriosclerosis, coronary arteritis, hepatitis, Behcet's disease, bladder cancer, prostatitis, pyelonephritis, glomerulonephritis, osteomyelitis, thyroiditis, uveitis, abdominal cavity inflammation, meningitis, pulmonary fibrosis and rheumatoid arthritis; and a method for screening for the HRF-related diseases.
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Thienopyranones as Kinase and Epigenetic Inhibitors (Fri, 14 Apr 2017)
<p id="p-0001" num="0000">The invention relates to methods of treating diseases including but not limited to, cancer, non-cancer proliferative disease, sepsis, autoimmune disease, viral infection, atheroscleosis, Type 1 or 2 diabetes, obesity, inflammatory disease, or Myc-depenent disorder including by modulating biological processes by the inhibition of PI3 kinase and/or bromodomain protein binding to substrates comprising the administration of a compound(s) of Formula I-IX (or pharmaceutically acceptable salts thereof) as defined herein.</p>
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COMPOSITION COMPRISING CYCLODEXTRIN AND BUDESONIDE DERIVATIVES FOR THE TREATMENT AND PROPHYLAXIS OF PULMONARY INFLAMMATIONS (Thu, 13 Apr 2017)
The present invention relates to novel and useful pharmaceutical compositions formulated with a cyclodextrin compound and a budesonide derivative for the treatment and/or prevention of pulmonary inflammatory disease. The present invention also relates to a novel and useful analytical technique for the detection and the quantification of ΗΡ-β-CD in solution. More specifically, the present invention relates to the use of a validated 1H NMR analysis for the detection and quantification of cyclodextrins directly in pharmaceutical formulations without any extraction or separation steps for liquid formulations.
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BIOMARKERS AND METHODS FOR MEASURING AND MONITORING AXIAL SPONDYLOARTHRITIS ACTIVITY (Fri, 07 Apr 2017)
<p id="p-0001" num="0000">Biomarkers useful for diagnosing and assessing inflammatory disease activity, for prediction of risk for progressive spinal and joint damage, in particular for axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS), and for generating a dataset are provided, along with kits for measuring expression of the biomarkers. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples.</p>
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BIOMARKERS AND METHODS FOR ASSESSING RESPONSE TO INFLAMMATORY DISEASE THERAPY WITHDRAWAL (Fri, 07 Apr 2017)
Provided herein are methods for assessing response to inflammatory disease therapy. The methods include placing a subject on a therapeutic regimen and subsequently performing an immunoassay to generate a score based on quantitative data for expression of biomarkers relating to inflammatory biomarkers. The methods further include recommending that the subject either remains on the therapeutic regimen, or is removed from the therapeutic regimen, based on the score.
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SUBSTITUTED PYRIDINE-2-CARBOXAMIDE COMPOUNDS AS APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS (Thu, 06 Apr 2017)
The present invention relates to compounds of Formula (I): Wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase ("ASK1") inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.
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Amyloid beta peptides as therapy for multiple sclerosis (Wed, 05 Apr 2017)
<p id="p-0001" num="0000">The invention provides methods for treating inflammatory diseases by administering to the subject an effective amount of an amyloid beta peptide, where the dose is effective to suppress or prevent initiation, progression, or relapses of disease, including the progression of established disease.</p>
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1-((3S,4R)-4-(3-FLUOROPHENYL)-1-(2-METHOXYETHYL)PYRROLIDIN-3-YL)-3-(4-METHYL-3-(2-METHYLPYRIMIDIN-5-YL)-1-PHENYL-1H-PYRAZOL-5-YL)UREA AS A TRKA KINASE INHIBITOR (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Provided is Compound (I) or a pharmaceutically acceptable salt thereof, which is an inhibitor of TrkA kinase and is useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation and inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, pelvic pain syndrome, diseases related to an imbalance of the regulation of bone remodeling, and diseases resulting from Connective Tissue Growth Factor aberrant signaling.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.43mm" wi="66.72mm" file="US20170087156A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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AMINE DERIVATIVES AS POTASSIUM CHANNEL BLOCKERS (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to compounds useful in the modulation of potassium channel activity in cells, in particular the activity of Kv1.3 channels found in T cells. The invention also relates to the use of these compounds in the treatment or prevention of autoimmune and inflammatory diseases, including multiple sclerosis, pharmaceutical compositions containing these compounds and methods for their preparation.</p>
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BENZIMIDAZOLES FOR USE IN THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES (Fri, 31 Mar 2017)
Provided herein are methods for treating, preventing, or ameliorating one or more symptoms of a condition, disorder, or disease mediated by a lipid kinase or a protein kinase with benzimidazoles, for example, of Formula I or II, and pharmaceutical compositions thereof. Also provided herein are benzimidazoles, and pharmaceutical compositions thereof; and methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.
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METHODS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES USING CEREBLON AS A PREDICTOR (Fri, 31 Mar 2017)
Uses of the protein cereblon as a predictor of clinical sensitivity to cancer, inflammatory diseases, and patient response to drug treatment.
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PURINONE COMPOUNDS AS KINASE INHIBITORS (Thu, 30 Mar 2017)
Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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COMPOUNDS FOR THE MODULATION OF RIP2 KINASE ACTIVITY (Fri, 24 Mar 2017)
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.
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CARBORANE COMPOUNDS AND METHODS OF USE THEREOF (Fri, 24 Mar 2017)
Disclosed herein are compounds comprising dicarba-closo-dodecaborane. The compounds can be, for example, estrogen receptor beta (ERβ) agonists. In some examples, the compounds can be selective ERβ agonists. Also provided herein are methods of treating, preventing, or ameliorating cancer in a subject, suppressing tumor growth in a subject, treating an inflammatory disease in a subject, treating a neurodegenerative disease in a subject, treating a psychotropic disorder in a subject, or a combination thereof, by administering to a subject a therapeutically effective amount of one or more of the compounds or compositions described herein, or a pharmaceutically acceptable salt thereof.
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TRICYCLIC COMPOUND AND JAK INHIBITOR (Thu, 23 Mar 2017)
Novel tricyclic compounds which have JAK inhibitory activities are useful for prevention, treatment or improvement of autoimmune diseases, inflammatory diseases and allergic diseases are provided. Novel tricyclic compound represented by the formula (I), the formula (II) or the formula (III) (wherein : each of A 1 , A 2 and A 3 is a cyclohexane-1,4-diyl group or the like; each of L 1 , L 2 and L 3 is a methylene group or the like; each of X 1 and X 3 is O or NH; each of R 1 and R 3 is a cyano C 1-6 haloalkyl group or the like; and R 2 is an aromatic heterocyclic group), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof.
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SUPRAMETALLOGELS AND USES THEREOF (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The disclosure provides nanostructures (e.g., nanospheres and nano-paddlewheels) formed through transition metal-ligand (e.g., Pd(II)-, Ni(II)-, or Fe(II)-ligand of Formula (A)) coordination and junction self-assembly. The disclosure also provides supramolecular complexes that include the nanostructures connected by divalent linkers Y. The provided supramolecular complexes are able to form gels (e.g., hydrogels). The gels are suprametallogels and exhibited excellent mechanical properties without sacrificing self-healing and showed high robustness and storage modulus. The present disclosure further provides compositions (e.g., gels) that include the nanostructures or supramolecular complexes and optionally an agent (e.g., small molecule), where the nanostructures and the nanostructure moieties of the supramolecular complexes may encapsulate and slowly release the agent. The nanostructures, supramolecular complex, and compositions may be useful in delivering an agent to a subject, tissue, or cell, as super-absorbent materials, and in treating a disease (e.g., a genetic diseases, proliferative disease (e.g., cancer or benign neoplasm), hematological disease, neurological disease, gastrointestinal disease (e.g., liver disease), spleen disease, respiratory disease (e.g., lung disease), painful condition, genitourinary disease, musculoskeletal condition, infectious disease, inflammatory disease, autoimmune disease, psychiatric disorder, or metabolic disorder).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="57.07mm" wi="51.05mm" file="US20170073311A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Biomarkers and Methods for Measuring and Monitoring Inflammatory Disease Activity (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Biomarkers useful for diagnosing and assessing inflammatory disease are provided, along with kits for measuring their expression. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples. The biomarkers include at least two biomarkers selected from the DAIMRK group and the score is a disease activity index (DAI).</p>
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IL-17A/F HETEROLOGOUS POLYPEPTIDES AND THERAPEUTIC USES THEREOF (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention is directed to a novel naturally occurring human cytokine that is comprised of a heterodimer of interleukin-17 and interleukin-17F designated herein as interleukin 17A/F (IL-17A/F). Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, specific antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.</p>
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INHIBITORS OF CYCLIN-DEPENDENT KINASES (Fri, 17 Mar 2017)
The present invention provides novel compounds of Formulae (I'), (I), (II'), and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK7, CDK12, or CDK13), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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SUBSTITUTED AMINO TRIAZOLES USEFUL AS HUMAN CHITINASE INHIBITORS (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">Disclosed are amino triazole compounds substituted with a piperidinyl ring that is itself substituted with a heterocyclic ring. These compounds are inhibitors of acidic mammalian chitinase and chitotriosidase. Also disclosed are methods of using the compounds to treat asthma reactions caused by allergens, as well as acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer.</p>
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SALTS AND SOLID FORM OF A BTK INHIBITOR (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">Disclosed herein are processes for preparing 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile free base (compound (I)), salts of compound (I) and solid state form of said salts. Also disclosed herein are pharmaceutical compositions comprising such salts and solid state form thereof and methods of treating cancer, autoimmune, and inflammatory diseases using compound (I) or a pharmaceutically acceptable salt thereof.</p>
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Fumarate analogs and uses thereof (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">Aspects of the present disclosure include compounds that find use for the treatment of a variety of autoimmune and inflammatory diseases and disorders. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.</p>
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WITHAFERIN A ANALOGS AND USES THEREOF (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention provides a novel class of withanolides that have been isolated from <i>W. somnifera </i>under aeroponic conditions or produced semi-synthetically from withanolide natural products. The invention also provides pharmaceutical compositions thereof and methods for using the same in proliferative diseases, neurodegenerative diseases, autoimmune, and inflammatory diseases.</p>
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AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="53.17mm" file="US20170066722A1-20170309-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">V is N or CR<sub>3</sub>;</li> <li id="ul0002-0003" num="0000">X is N or CR<sub>4</sub>;</li> <li id="ul0002-0004" num="0000">Y is N or CR<sub>5</sub>;</li> <li id="ul0002-0005" num="0000">Z is N or CR<sub>6</sub>;</li> <li id="ul0002-0006" num="0000">B is —(C═O)R<sub>1</sub>, a 5- to 10-membered heteroaryl group, or a group</li> <li id="ul0002-0007" num="0000">-L′″-NRR′, wherein R and R′ are the same or different and each represents a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group;</li> <li id="ul0002-0008" num="0000">R<sub>1 </sub>is a 5- to 10-membered heterocyclyl group, or —OR′, wherein R′ is a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group, or R<sub>1 </sub>is a proteinogenic α amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the α amino group, which amino acid is optionally esterified at the α carboxylic acid group with a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>6</sub>-C<sub>10 </sub>aryl group, or R<sub>1 </sub>is —NR″R′″, —NR<sup>IV</sup>-L′″-CONR″R′″, or —NR<sup>IV</sup>-L′″-COOR, wherein R, R″, R′″ and R<sup>IV </sup>are the same or different and each represents a hydrogen atom, a C<sub>1</sub>-C<sub>6 </sub>alkyl group or a C<sub>1</sub>-C<sub>6 </sub>haloalkyl group;</li> <li id="ul0002-0009" num="0000">either (a) W is N and R<sub>9 </sub>and R<sub>2 </sub>together form a bond, or (b) W is CR<sub>8</sub>, R<sub>8 </sub>and R<sub>9 </sub>together form a bond and R<sub>2 </sub>is a hydrogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>6</sub>-C<sub>10 </sub>aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl, -L′-A<sub>2</sub>, C<sub>3</sub>-C<sub>10 </sub>cycloalkyl, or —COOR′ group, wherein R′ is a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group, or, when Z is a moiety CR<sub>6</sub>, R<sub>2 </sub>may form, together with R<sub>6 </sub>and the carbon and nitrogen atoms which connect R<sub>2 </sub>and R<sub>6 </sub>in the formula (I), a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0010" num="0000">R<sub>3 </sub>is a hydrogen atom, a halogen atom, or a hydroxy, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy, nitro, or —NR′R″ group, wherein R′ and R″ are the same or different and each represent a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group;</li> <li id="ul0002-0011" num="0000">R<sub>4 </sub>and R<sub>5 </sub>are the same or different and each represent a hydrogen atom, a halogen atom, or a hydroxyl, C<sub>1</sub>-C<sub>8 </sub>alkyl, C<sub>1</sub>-C<sub>8 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy, nitro, —NR′R″, —CO<sub>2</sub>R′″, C<sub>6</sub>-C<sub>10 </sub>aryl, 5- to 10-membered heteroaryl, 5 to 10-membered heterocyclyl, or —CO—(C<sub>1</sub>-C<sub>6 </sub>alkyl) group, wherein R′, R″ and R′″ are the same or different and each represent a hydrogen atom or C<sub>1</sub>-C<sub>6 </sub>alkyl group, or R<sub>4 </sub>and R<sub>5 </sub>and the carbon atoms bonded to R<sub>4 </sub>and R<sub>5 </sub>together form a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0012" num="0000">R<sub>6 </sub>is a hydrogen atom, a halogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, C<sub>1</sub>-C<sub>6 </sub>haloalkoxy or —CO<sub>2</sub>R′ group, wherein R′ is hydrogen or C<sub>1</sub>-C<sub>6 </sub>alkyl, or, when W is a moiety CR<sub>8</sub>, R<sub>6 </sub>may form, together with R<sub>2 </sub>and the carbon and nitrogen atoms which connect R<sub>6 </sub>and R<sub>2 </sub>in the formula (I), a 5- to 6-membered heterocyclic ring;</li> <li id="ul0002-0013" num="0000">R<sub>7 </sub>is a hydrogen atom, a halogen atom, or a C<sub>1</sub>-C<sub>6 </sub>alkyl, or C<sub>1</sub>-C<sub>6 </sub>haloalkyl group,</li> <li id="ul0002-0014" num="0000">A<sub>2 </sub>represents a C<sub>6</sub>-C<sub>10 </sub>aryl or 5- to 10-membered heteroaryl group;</li> <li id="ul0002-0015" num="0000">L′, and L′″ are the same or different and each represent a C<sub>1</sub>-C<sub>6 </sub>alkylene, C<sub>2</sub>-C<sub>6 </sub>alkenylene, or C<sub>2</sub>-C<sub>6 </sub>alkynylene group;</li> <li id="ul0002-0016" num="0000">said aryl, heteroaryl, cycloalkyl and heterocyclyl groups being unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, C<sub>1</sub>-C<sub>4 </sub>alkyl, C<sub>1</sub>-C<sub>4 </sub>hydroxyalkyl, C<sub>1</sub>-C<sub>4 </sub>alkoxy, C<sub>1</sub>-C<sub>4 </sub>haloalkyl, C<sub>1</sub>-C<sub>4 </sub>haloalkoxy, —SOR, —SO<sub>2</sub>R, —NR′R″, —NR′(C═O)R″, —COOR, nitro and cyano substituents, wherein R, R′ and R″ are the same or different and each represents a hydrogen atom or C<sub>1</sub>-C<sub>4 </sub>alkyl group.</li> </ul> </li> </ul> </p>
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Cyclic compounds (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention provides compounds having a Toll-like receptor 4 (TLR4) signaling inhibitory action useful as preventive and therapeutic drugs of inflammatory disease and/or central nervous system disease or diseases such as chemotherapy-induced peripheral neuropathy (CIPN), chemotherapy-induced neuropathic pain (CINP), liver injury, ischemia-reperfusion injury (IRI) and the like. The present invention relates to a compound represented by formula (I) and a salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.14mm" wi="60.03mm" file="US09828357-20171128-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein, each symbol is explained in greater detail in the specification. </p>
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Polyfluorinated compounds acting as bruton tyrosine kinase inhibitors (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.</p>
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SUBSTITUTED AMINO TRIAZOLES USEFUL AS HUMAN CHITINASE INHIBITORS (Fri, 10 Mar 2017)
Disclosed are amino triazole compounds substituted with a piperidinyl ring that is itself substituted with a heterocyclic ring. These compounds are inhibitors of acidic mammalian chitinase and chitotriosidase. Also disclosed are methods of using the compounds to treat asthma reactions caused by allergens, as well as acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer.
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MALT1 INHIBITORS AND USES THEREOF (Fri, 10 Mar 2017)
Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin' s lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis,an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).
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HETEROCYCLIC COMPOUNDS (Fri, 10 Mar 2017)
The present invention provides a heterocyclic compound a TLR7 and/or TLR9 and/or TLR-7/8/9 and/or TLR-7/8 and/or TLR-7/9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases and/or inflammatory diseases and the like, in particular, acute decompensated heart failure, non-alcoholic steatohepatitis (NASH), IgA nephropathy, Duchenne muscular dystrophy (DMD), systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease, asthma, type 1 diabetes, myasthenia gravis, hematopoetic disfunction, B-cell malignancies, transplant rejection and graft-versus-host disease, hepatocellular carcinoma (HCC) and the like. The present invention is a compound represented by the formula (1) : wherein each symbol is as described in the specification, or a salt thereof.
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Site directed mutagenesis of trem-1 antibodies for decreasing viscosity (Fri, 10 Mar 2017)
Antibodies that are capable of specifically binding and preventing the activation of TREM-1, a protein expressed on monocytes, macrophages and neutrophils with both good affinity and low viscosity at clinically relevant concentrations are described. Such antibodies find utility in the treatment of individuals with an inflammatory disease, such as rheumatoid arthritis and inflammatory bowel disease.
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POLYFLUORINATED COMPOUNDS ACTING AS BRUTON'S TYROSINE KINASE INHIBITORS (Thu, 09 Mar 2017)
Provided herein are novel multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof, methods for preparing the same, and therapeutic methods by administering the compounds and formulation thereof to treat and inhibit autoimmune diseases or disorders, heteroimmune diseases or disorders, inflammatory diseases and cancers or disorders.
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TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-1(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP-ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.</p>
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The present invention discloses compounds according to Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.54mm" wi="69.85mm" file="US20170057928A1-20170302-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Cy, R<sup>1</sup>, L<sub>1</sub>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, L<sub>a</sub>, and R<sup>a </sup>are as defined herein.</p> <p id="p-0004" num="0000">Novel benzimidazoles according to Formula I, able to inhibit JAK are disclosed, these compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, allergic diseases, inflammatory diseases, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or hypersecretion of interferons.</p>
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Pyrazolyl-ureas as kinase inhibitors (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">There are provided compounds of formula (I) as defined in the specification, which are p38 MAP kinase inhibitors for use as medicaments for the treatment inter alia of inflammatory diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.41mm" wi="73.91mm" file="US09884845-20180206-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SIALYLTRANSFERASE INHIBITORS AND USES THEREOF (Fri, 03 Mar 2017)
Disclosed herein are novel sialyltransferase inhibitors, and compositions and methods for treating diseases and/or conditions associated with the activation of sialyltransferase, such as a cancer, an immune disease or an inflammatory disease.
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NOVEL TRICIN DERIVATIVE AND MEDICAL USE THEREOF (Wed, 01 Mar 2017)
The present invention relates to a novel tricin derivative isolated from Zizania latifolia Turcz., and to a medical use thereof. More specifically, the novel tricin derivative salcolin D isolated from Zizania latifolia Turcz. which is a natural ingredient is safe without cytotoxicity, and more effectively inhibits excessive production of NO which is a factor causing inflammatory diseases, compared to previously known tricin derivatives. In addition, the novel tricin derivative is also excellent in preventing release of -hexosaminidase which induces allergy, and thus can be used in anti-inflammatory drugs, anti-allergic drugs, or compositions for preventing or treating inflammatory allergic diseases. COPYRIGHT KIPO 2017
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INHIBITING THE TRANSIENT RECEPTOR POTENTIAL A1 ION CHANNEL (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to compounds of the Formula (I), or a pharmaceutically acceptable salt, pharmaceutical preparation, or pharmaceutical composition thereof, and their use for the treatment of pain, inflammatory disease, neuropathy, dermatological disorders, pulmonary conditions, and cough, as well as inhibiting the Transient Receptor Potential A1 ion channel (TRPA1).</p>
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INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
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Tetrahydrooxepinopyridine compound (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">[Problem] Provided is a compound having a positive allosteric modulating activity (PAM activity) on an α7 nicotinic acetylcholine receptor (α7 nACh receptor).</p> <p id="p-0002" num="0000">[Means for Solution] The present inventors have studied on a PAM activity on an α7 nACh receptor, and they have found that a tetrahydrooxepinopyridine compound has a PAM activity on an α7 nACh receptor, thereby completing the present invention. The tetrahydrooxepinopyridine compound of the present invention has a PAM activity on an α7 nACh receptor and can be expected as an agent for preventing or treating dementia, cognitive impairment, schizophrenia, Alzheimer's disease, CIAS, negative symptoms of schizophrenia, inflammatory diseases, or pain.</p>
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METHOD OF PROVIDING MONOCLONAL AUTO-ANTIBODIES WITH DESIRED SPECIFICITY (Fri, 24 Feb 2017)
<p id="p-0001" num="0000">Provided are novel binding molecules of human origin, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize antigens such as native endogenous proteins associated with, e.g., immune response, autoimmune disorders, inflammatory diseases, metabolic disorders, vascular function, neurodegenerative diseases or tumors. More particularly, a human Auto-Immunosome and corresponding monoclonal antibody reservoir are provided. In addition, pharmaceutical compositions, kits and methods for use in diagnosis and therapy of are described.</p>
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CYCLOPROPYLDERIVATIVES AND THEIR USE AS KINASE INHIBITORS (Fri, 24 Feb 2017)
The invention generally relates to cyclic compounds and, more particularly, to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof and pharmaceutical comopositions comprising the multicyclic compounds. The invention also relates to a method for treating a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T-Cell mediated autoimmune disesase) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.
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3-(PYRIDIN-3-YL)-ACRYLAMIDE AND N-(PYRIDIN-3-YL)-ACRYLAMIDE DERIVATIVES AND THEIR USE AS PAK OR NAMPT MODULATORS (Fri, 24 Feb 2017)
The invention generally relates to cyclic compounds and, more particularly, to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the multicyclic compounds. The invention also relates to a method for treating a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T- Cell mediated autoimmune diseases) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.
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(S,E)-3-(6-AMINOPYRIDIN-3-YL)-N-((5-(4-(3-FLUORO-3-METHYLPYRROLIDINE-1-CARBONYL)PHENYL)-7-(4-FLUOROPHENYL)BENZOFURAN-2-YL)METHYL)ACRYLAMIDE FOR THE TREATMENT OF CANCER (Fri, 24 Feb 2017)
The invention generally relates to substituted benzofuranyl compounds and, more particularly, to a compound represented by Structural Formula la: (I) or a pharmaceutically acceptable salt thereof. The invention also includes the synthesis and use of the compound of Structural Formula la, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of diseases or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T-Cell mediated autoimmune disesase) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.
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TETRA-O-SUBSTITUTED BUTANE-BRIDGE MODIFIED NDGA DERIVATIVES, THEIR SYNTHESIS AND PHARMAECUTICAL USE (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to nordihydroguaiaretic acid derivative compounds, namely, butane bridge modified nordihydroguaiaretic acid (NDGA) compounds and butane bridge modified tetra-O-substituted NDGA compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them and kits including them for the treatment of diseases and disorders, in particular, diseases resulting from or associated with a virus infection, such as HIV infection, HPV infection, or HSV infection, an inflammatory disease, such as various types of arthritis and inflammatory bowel diseases, metabolic diseases, such as diabetes and hypertension, or a proliferative disease, such as diverse types of cancers.</p>
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Prostaglandin Receptor EP2 Antagonists, Derivatives, Compositions, and Uses Related Thereto (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.</p>
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Compounds I (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I),</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.21mm" wi="60.28mm" file="US09890160-20180213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and their pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers or N-oxides, which are inhibitors of SSAO activity. The invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the treatment of medical conditions wherein inhibition of SSAO activity is beneficial, such as inflammatory diseases and immune disorders. </p>
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Tricyclic compound and JAK inhibitor (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Novel tricyclic compounds which have JAK inhibitory activities are useful for prevention, treatment or improvement of autoimmune diseases, inflammatory diseases and allergic diseases are provided.</p> <p id="p-0002" num="0000">Novel tricyclic compound represented by the formula (I), the formula (II) or the formula (III) (wherein: each of A<sup>1</sup>, A<sup>2 </sup>and A<sup>3 </sup>is a cyclohexane-1,4-diyl group or the like; each of L<sup>1</sup>, L<sup>2 </sup>and L<sup>3 </sup>is a methylene group or the like; each of X<sup>1 </sup>and X<sup>3 </sup>is O or NH; each of R<sup>1 </sup>and R<sup>3 </sup>is a cyano C<sub>1-6 </sub>haloalkyl group or the like; and R<sup>2 </sup>is an aromatic heterocyclic group), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="111.34mm" wi="69.85mm" file="US09890165-20180213-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHENYLSULFONAMIDO-BENZOFURAN DERIVATIVES AND USES THEREOF IN THE TREATMENT OF PROLIFERATIVE DISEASES (Fri, 17 Feb 2017)
Described herein are phenylsulfonamido-benzofuran derivatives, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, methods, uses, and kits involving compounds of Formulae (I), (II), (III), (IV), (V), or (VI) for treating and/or preventing proliferative diseases (e.g. cancers, inflammatory diseases, and autoimmune diseases) in a subject. The compounds and pharmaceutical compositions as described herein inhibit at least one protein of the BCL-2 family in a biological sample or subject to treat and/or prevent a proliferative disease. In certain embodiments, compounds described herein are selective inhibitors of MCL-1, a BCL-2 family member protein.
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PHENYLSULFONAMIDO-BENZOFURAN DERIVATIVES AND USES THEREOF IN THE TREATMENT OF PROLIFERATIVE DISEASES (Fri, 17 Feb 2017)
Described herein are phenylsulfonamido-benzofuran derivatives, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, methods, uses, and kits involving compounds of Formulae (I), (II), (III), (IV), (V), or (VI) for treating and/or preventing proliferative diseases (e.g. cancers, inflammatory diseases, and autoimmune diseases) in a subject. The compounds and pharmaceutical compositions as described herein inhibit at least one protein of the BCL-2 family in a biological sample or subject to treat and/or prevent a proliferative disease. In certain embodiments, compounds described herein are selective inhibitors of MCL-1, a BCL-2 family member protein.
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METHODS OF TREATING CANCERS, IMMUNE AND AUTOIMMUNE DISEASES, AND INFLAMMATORY DISEASES BASED ON BTK OCCUPANCY AND BTK RESYNTHESIS RATE (Fri, 17 Feb 2017)
In an embodiment, therapeutic methods and uses of Bruton's Tyrosine Kinase (BTK) inhibitors for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.
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Phenylsulfonamido-benzofuran derivatives and uses thereof in the treatment of proliferative diseases (Fri, 17 Feb 2017)
Described herein are phenylsulfonamido-benzofuran derivatives, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, methods, uses, and kits involving compounds of Formulae (I), (II), (III), (IV), (V), or (VI) for treating and/or preventing proliferative diseases (e.g. cancers, inflammatory diseases, and autoimmune diseases) in a subject. The compounds and pharmaceutical compositions as described herein inhibit at least one protein of the BCL-2 family in a biological sample or subject to treat and/or prevent a proliferative disease. In certain embodiments, compounds described herein are selective inhibitors of MCL-1, a BCL-2 family member protein.
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Composition comprising cyclodextrin and budesonide derivatives for the treatment and prophylaxis of pulmonary inflammations (Thu, 16 Feb 2017)
The present invention relates to novel and useful pharmaceutical compositions formulated with a cyclodextrin compound and a budesonide derivative for the treatment and/or prevention of pulmonary inflammatory disease. The present invention also relates to a novel and useful analytical technique for the detection and the quantification of HP-gamma-CD in solution. More specifically, the present invention relates to the use of a validated 1H NMR analysis for the detection and quantification of cyclodextrins directly in pharmaceutical formulations without any extraction or separation steps for liquid formulations.
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NOVEL COMPOUND HAVING IMMUNE DISEASE TREATMENT EFFECT AND USE THEREOF (Thu, 16 Feb 2017)
The present invention relates to a novel compound capable of effectively preventing and treating immune diseases and a use thereof. The novel compound of the present invention has effects of inhibiting the formation of proinflammatory cytokines, increasing the activity of regulatory T cells having immunoregulatory functions, inhibiting the production of autoantibodies to regulate excessive immune responses, and inhibiting the differentiation to osteoclasts, and thus can be used for treating immune diseases, such as autoimmune diseases, inflammatory diseases, and transplant rejection diseases, which are caused by abnormal regulation of various kinds of immune responses.
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NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">[1,2,4]triazolo[1,5-a]pyridine compounds are disclosed that have a formula represented by the following:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US20170035738A1-20170209-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diseases involving cartilage degradation, bone and/or joint degradation, for example osteoarthritis; and/or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g. diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6 and transplantation rejection (e.g. organ transplant rejection) and proliferative diseases.</p>
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DRUG DELIVERY CONJUGATES FOR TREATING RESISTANT CANCER AND FOR USE IN COMBINATION THERAPY (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">Described herein are drug delivery conjugates for targeted therapy. In particular, described herein are drug delivery conjugates that include polyvalent linkers comprising one or more unnatural amino acids that are useful for treating cancers and inflammatory diseases. In some embodiments, the cancer is selected from the group consisting of a carcinoma, a sarcoma, a lymphoma, Hodgekin's disease, a melanoma, a mesothelioma, Burkitts lymphoma, a nasopharyngeal carcinoma, a leukemia, and a myeloma.</p>
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COMPOSITIONS AND METHODS FOR DELIVERY OF KINASE INHIBITING PEPTIDES (Fri, 10 Feb 2017)
<p id="p-0001" num="0000">The invention relates to compositions and methods for the treatment of inflammatory disease states. In particular, the invention relates to the use of a nanoparticle incorporated kinase inhibiting peptide to treat inflammatory disease states.</p>
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MOTILE SPERM DOMAIN CONTAINING PROTEIN 2 AND INFLAMMATION (Fri, 10 Feb 2017)
Disclosed herein are methods of treating, preventing, or reducing the incidence of an inflammatory disease or disorder and methods of inhibiting, preventing, or reducing the incidence of one or more activities in a cell with an inhibitor of a Motile Sperm Domain containing Protein 2 (MOSPD2). Also disclosed are inhibitors of MOSPD2 and pharmaceutical compositions containing MOSPD2 inhibitors.
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MANNOSE DERIVATIVES USEFUL FOR TREATING PATHOLOGIES ASSOCIATED WITH ADHERENT E. COLI (Fri, 10 Feb 2017)
The present invention relates to mannose derivatives of formula (I): wherein R1 represents H, CO-(C1-C6)-alkyl or CO-alkylaryl, Y represents a single bond, CH2, O, NR3, S, A represents O, NH or S, X represents H and X' represents OH or X and X' taken together with the carbon atom bearing them form a CO group, R2 represents H, a linear or branched (C1-C6 )-alkyl or CF3, R3 represents H, a C1-C6 alkyl, a CO-(C1-C6 )-alkyl, CF3 or COCF3, and R is as described in claim 1. The mannose derivatives of formulae (I) are useful for treating pathologies associated with the presence of adherent Escherichia coli (AEC), in particular inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis; a urinary tract infection, in particular painful bladder syndrome and cystitis, more particularly interstitial cystitis; irritable bowel syndrome; metabolic diseases such as metabolic obesity, diabetes, hypercholesterolemia; autoimmune inflammatory diseases; and colorectal cancer, in particular colon cancer.
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PYRAZOLE PYRIMIDINE DERIVATIVE AND USES THEREOF (Fri, 10 Feb 2017)
The present invention provides pyrazole pyrimidine derivatives which inhibit Casein kinase I (CKI) and/or lnterleukin-1 receptor-associated kinase 1 (IRAKI) and methods of their manufacture, compositions comprising them and uses thereof in methods of treating malignant disease and disorders and methods for treating inflammatory diseases and disorders.
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ANTAGONISTS OF THE GOLGI REASSEMBLY-STACKING PROTEIN OF 55 KDA (GRASP55) AND USES THEREOF (Fri, 10 Feb 2017)
The present invention relates to new compounds useful as antagonists of the Golgi reassembly-stacking protein of 55 k Da (Grasp55), and in particular to their use as a non-hormonal male contraceptive. The present invention also relates to these compounds for use as a medicament, in particular for the treatment or the prevention of a disease selected from the group consisting of cancer, metastases and an inflammatory disease.
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Motile sperm domain containing protein 2 and inflammation (Fri, 10 Feb 2017)
Disclosed herein are methods of treating, preventing, or reducing the incidence of an inflammatory disease or disorder and methods of inhibiting, preventing, or reducing the incidence of one or more activities in a cell with an inhibitor of a Motile Sperm Domain containing Protein 2 (MOSPD2). Also disclosed are inhibitors of MOSPD2 and pharmaceutical compositions containing MOSPD2 inhibitors.
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MMF-DERIVATIVES OF ETHYLENEGLYCOLS (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds, e.g. for use as a medicament. In particular, the present invention relates to novel prodrugs of monomethyl fumarate (MMF) suitable as a medicament, preferably in the treatment and/or prevention of systemic diseases, autoimmune diseases, inflammatory diseases, for example multiple sclerosis, rheumatoid arthritis and psoriasis.</p>
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NOVEL SULPHUR CONTAINING LIPIDS FOR USE AS FOOD SUPPLEMENT OR AS MEDICAMENT (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present disclosure relates to lipid compounds of the general formula (I): (I) wherein R<sub>1 </sub>is selected from a C<sub>10</sub>-C<sub>22 </sub>alkyl, a C<sub>10</sub>-C<sub>22 </sub>alkenyl having 1-6 double bonds, and a C<sub>10</sub>-C<sub>22 </sub>alkynyl having 1-6 triple bonds; R<sub>2 </sub>and R<sub>3 </sub>are the same or different substituents; Y is selected from sulphur, sulfoxide, and sulfone; and X represents a carboxylic acid or a derivative thereof, a carboxylic ester, a carboxylic anhydride or a carboxamide; or a pharmaceutically acceptable salt, complex or solvate thereof. The disclosure also relates to pharmaceutical compositions and lipid compositions comprising such compounds, and to such compounds for use as medicaments or for use in therapy, in particular for the treatment of diseases related to the cardiovascular, metabolic and inflammatory disease area.</p>
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Kinase inhibitor (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">There is provided a compound of formula VIIa,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="75.52mm" file="US09822076-20171121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein Q<sup>x </sup>represents —C(O)O—C<sub>1-4 </sub>alkyl, or a salt or protected derivative thereof, and other compounds that are useful in the preparation of compounds that have antiinflammatory activity (e.g., through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and has use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines. </p>
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Compositions and Methods for Treating Neoplasia, Inflammatory Disease and Other Disorders (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The invention features compositions and methods for treating or preventing a neoplasia. More specifically, the invention provides compositions and methods for disrupting the interaction of a BET family polypeptide comprising a bromodomain with chromatin (e.g., disrupting a bromodomain interaction with an acetyl-lysine modification present on a histone N-terminal tail).</p>
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HETEROCYCLIC COMPOUNDS AND USES THEREOF (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.</p>
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2-amino-benzimidazole derivatives and their use as 5-lipoxygenase and/or prostaglandin e synthase inhibitors (Fri, 03 Feb 2017)
The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X<sp>1</sp> and X<sp>2</sp> are independently, at each occurrence, CR<sp>5</sp> or N; Y is C<sb>1</sb>-C<sb>6</sb> alkylene, wherein alkylene is optionally substituted with one to two C<sb>1</sb>-C<sb>3</sb> alkyl groups; R<sp>1</sp> is selected from the group consisting of hydrogen, halogen, C<sb>1</sb>-C<sb>6</sb> alkoxy, -NH<sb>2</sb>, -NHR<sp>6</sp>, -NR<sp>7</sp>R<sp>8</sp> and -NH-(R<sp>9</sp>)<sb>n</sb>-R<sp>10</sp>, n being 0 or 1; R<sp>2</sp> is selected from the group consisting of hydrogen, halogen, C<sb>1</sb>-C<sb>6</sb> alkyl, -NH<sb>2</sb>, -NHR<sp>6</sp>, - NR<sp>7</sp>R<sp>8</sp> and -NH-(R<sp>9</sp>)<sb>n</sb>-R<sp>10</sp>; R<sp>3</sp> is selected from the group consisting of hydrogen, hydroxyl, OR<sp>11</sp>, -NR<sp>7</sp>R<sp>8</sp>, C<sb>1</sb>-C<sb>6</sb> alkoxy, C<sb>1</sb>-C<sb>6</sb> alkyl, C<sb>3</sb>-C<sb>10</sb> cycloalkyl, C<sb>1</sb>-C<sb>3</sb> haloalkyl, -C(O)NHR<sp>11</sp>, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R<sp>a</sp> groups; and R<sp>4</sp> is selected from the group consisting of -NH<sb>2</sb>, -N(R<sp>12</sp>)(V)<sb>p</sb>R<sp>13</sp>, - NH(V)<sb>p</sb>-OR<sp>14</sp>, -NHC(O)R<sp>15</sp>, and groups of formula la shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.
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Quinoline derivatives for the treatment of inflammatory diseases (Fri, 03 Feb 2017)
The present invention relates to a compound of formula (I) wherein: Formula (II) means an aromatic ring wherein V is C or N and when V is N; Q is N or O, provided that R" does not exist when Q is O; R' independently represent a hydrogen atom or a group chosen among a (C<sb>1</sb>-C<sb>3</sb>)alkyl group, a halogen atom, a hydroxy! group, a - COOR<sb>1</sb> group, a -NO2 group, a -NR<sb>1</sb>R<sb>2</sb> group, a morpholinyl or a morpholino group, a N- methylpiperazinyl group, a (Ci-C3)fluoroalkyl group, a -O-P(=O)-(OR<sb>3</sb>XOR<sb>4</sb>) group, a (C<sb>1</sb>-C<sb>4</sb>)alkoxy group and a -CN group, and can further be a group chosen among:(IIa), (IIIa) or anyone of its pharmaceutically acceptable salt, for use in the treatment and/or prevention of an inflammatory disease.
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Novel formulations of a Bruton's tyrosine kinase inhibitor (Fri, 03 Feb 2017)
Described herein is the Brutons tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including novel pharmaceutical formulations thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION COMPRISING SAME AS ACTIVE COMPONENT FOR PREVENTING OR TREATING INFLAMMATORY DISEASE (Fri, 03 Feb 2017)
The present invention relates to a novel compound exhibiting activity of inhibiting Leukotriene B4 receptor 2 (BLT2), and to a pharmaceutical composition comprising the same as an active component for preventing or treating an inflammatory disease. In the present invention, a novel compound exhibiting BLT2 inhibitory activity is investigated. The compound is experimentally confirmed to exhibit excellent effects of promoting apoptosis of cancer cells, suppressing cancer metastasis, suppressing chemotaxis, resisting against asthma, and the like, thereby enabling a fundamentally approaching target therapy for preventing or treating an inflammatory disease. COPYRIGHT KIPO 2017
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HETEROCYCLIC COMPOUND (Thu, 02 Feb 2017)
Provided is a compound having a superior PKC inhibitory action, and useful as a prophylactic or therapeutic agent for immune diseases, inflammatory diseases and the like, or a salt thereof. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a superior PKC inhibitory action, and is useful as a prophylactic or therapeutic agent for immune diseases, inflammatory diseases and the like.
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NATURAL AND SYNTHETIC COMPOUNDS FOR TREATING CANCER AND OTHER DISEASES (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">This invention provides a method of synthesizing new active compounds for pharmaceutical uses including cancer treatment, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers. This invention is an anti-adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. It modulates angiogenesis. The compounds also use as mediator of cell adhesion receptor, cell circulating, cell moving and inflammatory diseases. The compounds are attached with angeloyl, acetyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2-methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-cis-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, O—C(2-18) Acyl.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="54.53mm" wi="72.14mm" file="US20170022246A1-20170126-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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LICOFELONE DERIVATIVES AND METHODS OF USE (Fri, 27 Jan 2017)
Derivatives of licofelone for the treatment of chronic inflammatory diseases and epithelial cancers associated with chronic inflammation are disclosed. The agents target mPGES-1 and 5-LOX.
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OXADIAZOLE DERIVATIVES USEFUL AS HDAC INHIBITORS (Fri, 27 Jan 2017)
The present invention provide a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of autoimmune diseases and/or inflammatory diseases, graft versus host disease, cancers, central nervous diseases including neurodegenerative diseases, Charcot-Marie-Tooth disease and the like, and a pharmaceutical composition comprising the compound. The present invention relates to a compound represented by the formula (I) : wherein each symbol is as defined in the specification, or a salt thereof.
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THERAPEUTIC/PREVENTIVE AGENT CONTAINING COUMARIN DERIVATIVE AS ACTIVE INGREDIENT (Thu, 26 Jan 2017)
An object of the present invention is to provide a preventive or therapeutic agent for inflammatory diseases or degenerative intervertebral disk diseases. A coumarin derivative or a pharmaceutically acceptable salt or hydrate thereof which is an active ingredient of the preventive or therapeutic agent of the present invention exhibits an excellent suppressive action in a pharmacological test where production of inflammation-related factor such as inflammatory cytokine or fibrosis-related factor as an index. Moreover, said compound also exhibits an excellent suppressive action to pulmonary fibrosis model animals and degenerative intervertebral disk disease model animals. Accordingly, the present invention is very useful as a preventive or therapeutic agent for inflammatory diseases and degenerative intervertebral disk diseases.
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INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">Disclosed herein are amido compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
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HETEROCYCLIC COMPOUND (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention provide a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of autoimmune diseases and/or inflammatory diseases, graft versus host disease, cancers, central nervous diseases including neurodegenerative diseases, Charcot-Marie-Tooth disease and the like, and a pharmaceutical composition comprising the compound.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by the formula (I):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.28mm" wi="69.85mm" file="US20170015655A1-20170119-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as defined in the specification, or a salt thereof.</p>
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BROMODOMAIN INHIBITORS (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The present invention provides for compounds of formula (I) wherein R<sup>x</sup>, X, Y, Y<sup>1</sup>, L<sup>1</sup>, A<sup>1</sup>, A<sup>2</sup>, A<sup>3</sup>, A<sup>4</sup>, A<sup>5</sup>, A<sup>6</sup>, A<sup>7</sup>, and A<sup>8</sup>, have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.52mm" wi="58.08mm" file="US20170015673A1-20170119-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BIOMARKERS AND METHODS FOR MEASURING AND MONITORING JUVENILE IDIOPATHIC ARTHRITIS ACTIVITY (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">Biomarkers useful for assessing inflammatory disease or flare activity, in particular in juvenile idiopathic arthritis, are provided, along with kits for measuring expression of the biomarkers. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples.</p>
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PECTIN COMPOSITIONS FOR PREVENTING AND TREATING INFLAMMATORY DISEASES (Fri, 20 Jan 2017)
This invention relates generally to compositions and methods for combating inflammatory disease and particularly to the use of feed or food compositions for preventing, reducing and/or treating inflammatory disorders, diseases, or discomforts, wherein the compositions comprising at least one specific pectin.
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Pyrrolo[3,2-c]pyridine derivatives as TLR inhibitors (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The present invention provides a heterocyclic compound having a TLR7, TLR9, TLR7/8, TLR7/9 or TLR7/8/9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases, inflammatory diseases and the like, in particular, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.87mm" wi="59.77mm" file="US09643967-20170509-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as P38 MAP knase inhibitors (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">There are provided compounds of formula (I) which are inhibitors of the family of p38 mitogen-activated protein kinase enzymes, and to their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as asthma and COPD.</p>
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INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
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ARYL SULTAM DERIVATIVES AS RORc MODULATORS (Fri, 13 Jan 2017)
Compounds of the formula I: or a pharmaceutical salt thereof, wherein p, s, A, R3 and Re are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
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ARYL SULTAM DERIVATIVES AS RORc MODULATORS (Fri, 13 Jan 2017)
Compounds of the formula I, or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, X1, X2, X3, X4, Y, Z, A, Het, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are as defined herein.. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis, muscular sclerosis and psoriasis.
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HETEROBICYCLIC N-AMINOPHENYL-AMIDES AS INHIBITORS OF HISTONE DEACETYLASE (Fri, 13 Jan 2017)
This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula (I) or any one of Compounds 100-175) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.
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HETERO-HALO INHIBITORS OF HISTONE DEACETYLASE (Fri, 13 Jan 2017)
This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula I, II or any of Compounds 100-128 or any of those in Tables 2 or 3) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.
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1-((3S,4R)-4-(3-fluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(4-methyl-3-(2-methylpyrimidin-5-yl)-1-phenyl-1h-pyrazol-5-yl)urea as a TrkA kinase inhibitor (Fri, 13 Jan 2017)
Provided is Compound (I) or a pharmaceutically acceptable salt thereof, which is an inhibitor of TrkA kinase and is useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation and inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, pelvic pain syndrome, diseases related to an imbalance of the regulation of bone remodeling, and diseases resulting from Connective Tissue Growth Factor aberrant signaling.
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A novel compound isolated from Pseudolysimachion rotundum var. subintegrum containing abundant amount of active ingredient, the composition comprising the same for preventing or treating allergy disease, inflammatory disease, asthma or chronic obstructive pulmonary disease and the use thereof (Fri, 13 Jan 2017)
The present invention relates to a novel methanocyclopenta[e][1,3]dioxepin-7-yl 3,4-dihydroxybenzoate derivative (KS534) represented below as the Chemical Formula 1, the pharmaceutically acceptable salt or solvates thereof, a composition comprising the same as an active ingredient for preventing or treating allergic disease, inflammatory disease, asthma or chronic obstructive pulmonary disease (COPD) and the use thereof. Formula (1)
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A novel compound (KS 513) isolated from pseudolysimachion rotundum var. subintegrum, the composition comprising the same as an active ingredient for preventing or treating allergy disease, inflammatory disease, asthma or chronic obstructive pulmonary disease and the use thereof (Fri, 13 Jan 2017)
The present invention relates to a novel (1aS,1bS,2S,4S,5aR,6S,6aS)-1a-(hydroxymethyl)-4-methoxy-2-(((2S,3R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)octahydrooxireno[2',3':4,5]cyclopenta[1,2-c]pyran-6-yl 4-hydroxybenzoate} (KS-513), the isomer thereof, the pharmaceutically acceptable salt or solvates thereof, a composition comprising the same as an active ingredient for preventing or treating allergic disease, inflammatory disease, asthma or chronic obstructive pulmonary disease (COPD) and the use thereof.
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Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity (Fri, 13 Jan 2017)
This invention relates to substituted bicyclic dihydropyrimidinones of formula 1 and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other autoimmune and allergic disorders, allograft rejection, and oncological diseases.
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Derivatives of polyhydroxy compounds (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds, e.g. for use as a medicament. In particular, the present invention relates to novel prodrugs of monomethyl fumarate (MMF) suitable as a medicament, preferably in the treatment and/or prevention of systemic diseases, autoimmune diseases, inflammatory diseases, for example multiple sclerosis and psoriasis.</p>
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TARGETING AGENT ANTIBODY CONJUGATES AND USES THEREOF (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">Methods, compositions and uses are provided for bispecific antibodies comprising one or more unnatural amino acids. The bispecific antibodies may bind to two or more different receptors, co-receptors, antigens, or cell markers on one or more cells. The bispecific antibodies may be used to treat a disease or condition (e.g., cancer, autoimmune disease, pathogenic infection, inflammatory disease). The bispecific antibodies may be used to modulate (e.g., stimulate or suppress) an immune response.</p>
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USE OF CELL-FREE NUCLEOSOMES AS BIOMARKERS IN SPUTUM SAMPLES (Fri, 06 Jan 2017)
The invention relates to the use of a cell-free nucleosome as a biomarker in a sputum sample for the diagnosis or detection of cancer, adenoma, autoimmune disease or inflammatory disease. The invention also relates to methods of detecting said cell free nucleosomes in sputum samples, in particular in methods of diagnosis.
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USE OF CELL-FREE NUCLEOSOMES AS BIOMARKERS IN FECAL SAMPLES (Fri, 06 Jan 2017)
The invention relates to the use of a cell-free nucleosome as a biomarker in a fecal sample for the diagnosis or detection of cancer, adenoma, autoimmune disease or inflammatory disease. The invention also relates to methods of detecting said cell free nucleosomes in fecal samples, in particular in methods of diagnosis.
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PYRROLOPYRIMIDINE COMPOUNDS AS KINASE INHIBITORS (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">Disclosed herein are methods of using pyrrolo[2,3-d]pyrimidine Btk inhibitors, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, and inflammatory diseases or conditions.</p>
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Kinase inhibitors (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">There are provided compounds of formula IIb,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.68mm" wi="69.85mm" file="US09790174-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein LG<sup>1 </sup>represents imidazolyl, chloro or aryloxy, which compounds are useful in the preparation of compounds that have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines. </p>
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Bioactivity proanthocyanidin compound isolated from Lasia spinosa (L.) Thwait (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present invention disclosed a compound, proanthocyanidin A1 (PA1), which is isolated from <i>Lasia spinosa </i>(L.) Thwait, for its effects in shortening of clolon length, reducing colonic tissue damage, suppressing colonic myeloperoxidase activity with colitis. The said compound can be used in treating inflammatory diseases and anti-cancer leading compound.</p>
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COMPOSITION FOR TREATING OR PREVENTING INFLAMMATORY SKIN DISEASE, COMPRISING, AS ACTIVE INGREDIENT, IMMATURE CITRUS FRUIT EXTRACT, OR SYNEPHRINE OR SALT THEREOF (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to a composition for treating or preventing an inflammatory skin disease, comprising, as an active ingredient, an unripe <i>Citrus unshiu </i>fruit extract and/or Synephrine or salt thereof. The composition of the present invention prevents an inflammatory reaction by inhibiting activity of STAT6, expression of eotaxin-1 and an agglomeration function of eosinophil, and thus, shows effects of preventing and treating an allergic inflammatory disease, atopic dermatitis, eczema, psoriasis, etc. Also, the composition of the present invention does not have cytotoxicity and a skin side effect, and thus, can be safely applied to pharmaceutical products and cosmetics.</p>
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IL-18 binding molecules (Fri, 30 Dec 2016)
<p id="p-0001" num="0000">IL-18 participates in both innate and acquired immunity. The bioactivity of IL-18 is negatively regulated by the IL-18 binding protein (IL18BP), a naturally occurring and highly specific inhibitor. This soluble protein forms a complex with free IL-18 preventing its interaction with the IL-18 receptor, thus neutralizing and inhibiting its biological activity. The present invention discloses binding molecules, in particular antibodies or fragments thereof, which bind IL-18 and do not bind IL-18 bound to IL-18BP (IL-18/IL-18BP complex). Apart from its physiological role, IL-18 has been shown to mediate a variety of autoimmune and inflammatory diseases. The binding molecules of the inventions may be used as therapeutic molecules for treating IL-18-related autoimmune and inflammatory diseases or as diagnostic tools for characterizing, detecting and/or measuring IL-18 not bound to IL-18BP as component of the total IL-18 pool.</p>
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CRYSTALLINE L-ARGININE SALT OF (R)-2-(7-(4-CYCLOPENTYL-3-(TRIFLUOROMETHYL)BENZYLOXY)-1,2,3,4-TETRAHYDROCYCLO-PENTA[B]INDOL-3-YL)ACETIC ACID(COMPOUND1) FOR USE IN SIPI RECEPTOR-ASSOCIATED DISORDERS (Fri, 30 Dec 2016)
The present invention relates to, inter alia, a novel crystalline free- plate habit or morphology, processes for preparing the crystalline free-plate habit, and uses of the crystalline free-plate habit of the L- arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy) -l,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(Compound1) in the treatment of SIPjreceptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditionscharacterized byan underlying defect in the vascular integrity or that are associated with angiogenesis such as may be pathologic(e.g.,as may occur in inflammation, tumor development, and atherosclerosis).
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NOVEL 5-HT2 ANTAGONISTS (Fri, 30 Dec 2016)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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FUSED BICYCLIC PYRIMIDINE DERIVATIVES AND USES THEREOF (Fri, 30 Dec 2016)
The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDK12, or CDK13) or a lipid kinase such as a phosphatidylinositol- 5 -phosphate 4- kinase (PIP4K) (e.g., ΡΙ5Ρ4Κα, ΡΙ5Ρ4Κβ, or ΡΙ5Ρ4Κγ)) in the subject.
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4,6-PYRIMIDINYLENE DERIVATIVES AND USES THEREOF (Fri, 30 Dec 2016)
The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDK12, or CDK13) or a lipid kinase such as a phosphatidylinositol- 5 -phosphate 4- kinase (PIP4K) (e.g., ΡΙ5Ρ4Κα, ΡΙ5Ρ4Κβ, or ΡΙ5Ρ4Κγ)) in the subject.
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Crystalline L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(Compound1) for use in SIP1 receptor-associated disorders (Fri, 30 Dec 2016)
The present invention relates to, inter <i>alia</i>, a novel crystalline free- plate habit or morphology, processes for preparing the crystalline free-plate habit, and uses of the crystalline free-plate habit of the L- arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy) -l,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(Compound1) in the treatment of SIPjreceptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditionscharacterized byan underlying defect in the vascular integrity or that are associated with angiogenesis such as may be pathologic(<i>e.g</i>.,as may occur in inflammation, tumor development, and atherosclerosis).
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NOVEL 5-HT2 ANTAGONISTS (Thu, 29 Dec 2016)
The present invention relates to 1-amidino-3-aryl-2-pyrazoline derivatives of the general formula I The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT 2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, and other inflammatory diseases, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.
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N-CONTAINING HETEROCYCLIC COMPOUNDS (Thu, 29 Dec 2016)
The present invention relates to N-containing heterocyclic compounds that are inhibitors of protein kinases including JAK kinases. In particular, the compounds are selective for JAK1, JAK2, JAK3 or TYK2 kinases and combinations thereof such as JAK1 and JAK2. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.
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Inhibitor of p38 MAP kinase (Fri, 23 Dec 2016)
<p id="p-0001" num="0000">A compound of formula (XV):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.00mm" wi="68.07mm" file="US09624196-20170418-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1 </sub>represents an amino group, a protected amino group or nitro group; or a salt thereof. The compound is a p38 MAP kinase inhibitor. The compound and its pharmaceutically acceptable salts can be used for treatment of conditions, such as inflammatory diseases.</p>
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INHIBITORS OF C-JUN-N-TERMINAL KINASE (JNK) (Fri, 23 Dec 2016)
<p id="p-0001" num="0000">The present invention provides novel compounds according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.98mm" wi="70.36mm" file="US20160368910A1-20161222-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where Ring A, Ring B, X, L<sub>1</sub>, L<sub>2</sub>, R<sup>A</sup>, R<sup>C</sup>, R<sup>D</sup>, R<sup>E</sup>, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.</p>
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