Inflammatory diseases

SELECTIVE HISTONE DEACETYLASE INHIBITORS FOR THE TREATMENT OF HUMAN DISEASE (Fri, 13 Jul 2018)
Selective HDAC inhibitors, and pharmaceutical compositions that include the same, are described herein for the treatment of cancer, immunological diseases, inflammatory diseases, and neurological diseases.
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HETEROCYCLIC COMPOUND (Thu, 05 Jul 2018)
The present invention provides a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of inflammatory disease 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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DIMERS OF COVALENT NFKB INHIBITORS (Fri, 29 Jun 2018)
Provided herein are compounds and methods for modulating the NFĸB pathway. More particularly, provided are inhibitors of the NFĸB pathway and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer, autoimmune diseases, inflammatory diseases, diabetes, cardiovascular diseases, or neurological diseases.
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HETEROCYCLIC INHIBITORS OF MCT4 (Fri, 22 Jun 2018)
Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula (I). Methods of inhibition MCT4 activity in a human or animal subject are also provided.
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INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE (Fri, 22 Jun 2018)
Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.
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SUBSTITUTED PYRAZOLOAZEPIN-4-ONES AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS (Fri, 22 Jun 2018)
The present invention relates to novel substituted pyrazoloazepin-4-ones with phosphodiesterase inhibitory activity, as well as to their use as therapeutic agents the treatment of inflammatory diseases and conditions.
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SUBSTITUTED PYRAZOLOAZEPIN-4-ONES AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS (Fri, 22 Jun 2018)
The present invention relates to novel substituted pyrazoloazepin-4-ones with phosphodiesterase inhibitory activity, as well as to their use as therapeutic agents in the treatment of inflammatory diseases and conditions.
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SUBSTITUTED PYRAZOLOAZEPIN-8-ONES AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS (Fri, 22 Jun 2018)
The present invention relates to novel pyrazoloazepin-8-ones with phosphodiesterase inhibitory activity, as well as to their use as therapeutic agents in the treatment of inflammatory diseases and conditions.
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Tricyclic Derivative Compound, Method for Preparing Same, and Pharmaceutical Composition Comprising Same (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to novel tricyclic derivative compounds, and more specifically to tricyclic derivative compounds, optical isomers thereof, racemates thereof, or pharmaceutically acceptable salts thereof, which have excellent activity against PARP-1, tankyrase-1 or tankyrase-2. The tricyclic derivative compounds, optical isomers thereof, racemates thereof or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, and thus can be effectively used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer.</p>
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PYRAZOLOPYRIDINAMINES AS MKNK1 AND MKNK2 INHIBITORS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">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 and/or angiogenesis disorder, inflammatory disease and disease associated with inflammatory pain, as a sole agent or in combination with other active ingredients.</p>
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HETEROCYCLIC INHIBITORS OF MCT4 (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.33mm" wi="69.85mm" file="US20180162822A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Methods of inhibition MCT4 activity in a human or animal subject are also provided.</p>
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COMPOUNDS FOR THE MODULATION OF MYC ACTIVITY (Fri, 15 Jun 2018)
<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., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.34mm" wi="62.99mm" file="US20180162851A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR MODULATING SGK ACTIVITY, AND METHODS THEREOF (Fri, 15 Jun 2018)
The invention provides novel chemical compounds useful for treating one or more of autoimmune diseases, cancer, cardiovascular diseases, inflammatory diseases and diabetes, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
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Tetracyclic bromodomain inhibitors (Fri, 15 Jun 2018)
The present invention provides for compounds of formula (I) wherein R1 , R2 , R6, YI, y2, Y', A', A2 , A3 and A4 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 one or more compounds of formula (I).
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FUSED BICYCLIC PYRIMIDINE DERIVATIVES AND USES THEREOF (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">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., PI5P4Kα, PI5P4Kβ, or PI5P4Kγ)) in the subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.51mm" wi="71.54mm" file="US20180153894A1-20180607-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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EXOSOMES FOR DELIVERY OF THERAPEUTIC AGENTS (Fri, 08 Jun 2018)
The present invention provides exosomes as drug delivery vehicles, compositions comprising a therapeutic agent encapsulated within such exosomes, methods of producing such exosomes and compositions thereof, as well as methods of delivering such exosomes and compositions to a specific patient tissue or organ. The present invention also provides methods of treating a disease, disorder, or condition such as cancer, an inflammatory disease, an infectious disease, an allergic disease, or an autoimmune disease, comprising administering to a patient in need thereof a provided therapeutic-loaded exosome or a pharmaceutical composition thereof.
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INHIBITORS OF CYCLIN-DEPENDENT KINASE 12 (CDK12) AND USES THEREOF (Fri, 01 Jun 2018)
The present invention provides novel compounds of Formulae (I') 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., CDK12), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES AND USES THEREOF (Fri, 01 Jun 2018)
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 and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma)), 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 an interleukin-1 receptor-associated kinase (IRAK) (e.g., IRAKI and/or IRAK4) in the subject.
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NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION, FOR PREVENTING OR TREATING INFLAMMATORY DISEASES, COMPRISING SAME AS ACTIVE INGREDIENT (Thu, 31 May 2018)
The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, comprising same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.
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NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION, FOR PREVENTING OR TREATING INFLAMMATORY DISEASES, COMPRISING SAME AS ACTIVE INGREDIENT (Thu, 31 May 2018)
The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, comprising same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.
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HETEROCYCLIC COMPOUND (Thu, 31 May 2018)
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 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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NOVEL COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">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.</p>
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PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING ARTHRITIS OR INFLAMMATORY DISEASE CONTAINING 2-METHOXY-4-(3-(4-METHOXYPHENYL)PROPYL-1-EN-1-YL)PHENOL AS ACTIVE INGREDIENT (Fri, 18 May 2018)
<p id="p-0001" num="0000">Disclosed herein is a pharmaceutical composition for treating or preventing inflammatory diseases or arthritis, which includes 2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition exhibits superior therapeutic efficacy against arthritis without any side effects such as toxicity, etc.</p>
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INHIBITORS OF ALPHA-AMINO-BETA-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE (Fri, 18 May 2018)
<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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1-PYRAZOLYL-3- (4- ((2 -ANILINOPYRIMIDIN- 4 - YL) OXY) NAPTHTHALEN- I - YL) UREAS AS P38 MAPKINASE INHIBITORS (Fri, 18 May 2018)
<p id="p-0001" num="0000">There is provided a compound of formula (I) which is an inhibitor of the family of p38 mitogen-activated protein kinase enzymes, and to its 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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SERINE/THREONINE KINASE INHIBITORS (Thu, 17 May 2018)
Compounds of Formula I or a stereoisomer, tautomer, prodrug 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, prodrug 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.
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BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Thu, 17 May 2018)
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, MNK1a, 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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EXTRACTS OF ANDROGRAPHIS PANICULATA, METHODS FOR PREPARATION AND USE THEREOF (Sat, 12 May 2018)
Disclosed herein are extracts of Andrographis paniculata having highly concentrated active ingredients, preparation methods and medical use for treating autoimmunity and inflammatory disease.
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EXTRACTS OF ANDROGRAPHIS PANICULATA, METHODS FOR PREPARATION AND USE THEREOF (Sat, 12 May 2018)
Disclosed herein are extracts of Andrographis paniculata having highly concentrated active ingredients, preparation methods and medical use for treating autoimmunity and inflammatory disease.
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PYRIDAZINE DERIVATIVES AS RORC MODULATORS (Sat, 12 May 2018)
Compounds of formula (I): (I) or pharmaceutical salts thereof, wherein m, n,, p, q A, B, Ri, R2, R3, R4, R5, R6and R7are as defined herein. Also disclosed are methods of making the compounds and using the compounds as RORs modulators for treatment of inflammatory diseases such as arthritis.
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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS (Fri, 11 May 2018)
<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="50.46mm" wi="69.85mm" file="US20180127425A1-20180510-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<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, W, X, Y, Z, 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.</li> </ul> </li> </ul> </p>
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NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN, 3BETA-25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVERS DISEASES AND ATHEROSCLEROSIS (Fri, 11 May 2018)
<p id="p-0001" num="0000">5-cholesten, 3β,25-diol, disulfate (25HCDS) has been found to be an authentic PPARγ 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.</p>
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GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, and methods of using the same, e.g., to treat autoimmune or inflammatory diseases.</p>
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TERT-BUTYL N-[2-{4-[6-AMINO-5-(2,4-DIFLUOROBENZOYL)-2-OXOPYRIDIN-1(2H)-YL]-3,5- DIFLUOROPHENYL}ETHYL]-L-ALANINATE OR A SALT,HYDRATE OR SOLVATE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention provides a compound which is: tert-butyl N-[2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alaninate or a salt, hydrate or solvate thereof. The present invention also provides a pharmaceutical composition comprising the compound together with one or more pharmaceutically acceptable carriers and/or excipients. The compound and composition are useful for inhibiting the activity of a p38 MAP kinase enzyme. As such they may be used in the treatment of a autoimmune or inflammatory disease, or a cell proliferative disease. In addition, the invention provides an acid produced by hydrolysis of the ester group of the compound of the invention. The acid is N-[2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alanine.</p>
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SERINE/THREONINE KINASE INHIBITORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compounds of Formula I or a stereoisomer, tautomer, prodrug 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, prodrug 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="29.29mm" wi="62.06mm" file="US20180127393A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Processes for preparing JAK inhibitors and related intermediate compounds (Fri, 11 May 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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NOVEL COMPOUND HAVING IMMUNE DISEASE TREATMENT EFFECT AND USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">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 production of inflammatory cytokines, increasing the activity of regulatory T cells having immunoregulatory functions, inhibiting the production of auto-antibodies to regulate excessive immune responses, and inhibiting the differentiation of osteoclasts, and thus can be used for treating immune diseases, such as autoimmune disease, inflammatory disease, and transplant rejection diseases, which are caused by abnormal regulation of various kinds of immune response</p>
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CYCLIC COMPOUND (Fri, 04 May 2018)
<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 autoimmune disease and/or inflammatory disease or diseases such as chemotherapy-induced peripheral neuropathy (CIPN), chemotherapy-induced neuropathic pain (CINP), liver injury, ischemia-reperfusion injury (IRI) and the like.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by formula (I) and a salt thereof:</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.29mm" wi="61.81mm" file="US20180118708A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">(wherein, each symbol is explained in greater detail in the specification).</p>
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lAP E3 LIGASE DIRECTED PROTEOLYSIS TARGETING CHIMERIC MOLECULES (Fri, 04 May 2018)
<p id="p-0001" num="0000">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.</p>
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NEW COMPOUNDS I (Fri, 04 May 2018)
<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="US20180118744A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">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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COMPOUNDS (Fri, 04 May 2018)
<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="65.45mm" wi="69.85mm" file="US20180118754A1-20180503-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 compounds and their compositions in treatment, for example in the treatment of inflammatory diseases, in particular respiratory inflammatory disease. The invention also extends to methods of making said compounds.</p>
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PYRAZOLYL UREAS AS KINASE INHIBITORS (Fri, 04 May 2018)
<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>
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N,N'-DIARYLUREA, N,N'-DIARYLTHIOUREA AND N,N'-DIARYLGUANIDINO COMPOUNDS FOR USE IN TREATMENT AND PREVENTION OF INFLAMMATORY DISEASE (Fri, 04 May 2018)
A compound according to formula (I) wherein L is CH2−O, CH2−S, CH2−CH2, or CH=CH; R1 and R2 are independently selected out of H, halogen, C1 to C3 alkyl, halogenated C1 to C3 alkyl, C1 to C3 alkyloxy, or halogenated C1 to C3 alkyloxy; Ar is an aryl moiety, preferably phenyl or naphthyl, or a moncyclic- or bicyclic heteroaryl moiety, wherein optionally the aryl or heteroaryl moiety is further substituted; X is O, S, or NR3, wherein R3 is H, C1 to C3 alkyl, halogenated C1 to C3 alkyl, or tert-butyloxycarbonyl; Y is O, S, NR4 or N(R4)R5, wherein R4 and R5 are independently selected out of H or C1 to C3 alkyl; and wherein if Y is O, S, or NR4, then both A are NH, and the punctuated bonds represent a double bond to Y and single bonds to each A; or wherein if Y is N(R4)R5, then one A is N, the other A is NH, and the punctuated bonds represent a double bond to the A being N, a single bond to the A being NH and a single bond to Y; and use of such a compound in treatment or prevention of an inflammatory disease or an inflammation-related disorder.
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N,N' -DIARYLUREA, N,N' -DIARYLTHIOUREA AND N,N' -DIARYLGUANIDINO COMPOUNDS FOR USE IN TREATMENT AND PREVENTION OF INFLAMMATORY DISEASE (Thu, 03 May 2018)
A compound according to formula I wherein L is CH 2 -O, CH 2 -S, CH 2 -CH 2 , or CH=CH; R 1 and R 2 are independently selected out of H, halogen, C1 to C3 alkyl, halogenated C1 to C3 alkyl, C1 to C3 alkyloxy, or halogenated C1 to C3 alkyloxy; Ar is an aryl moiety, preferably phenyl or naphthyl, or a moncyclic- or bicyclic heteroaryl moiety, wherein optionally the aryl or heteroaryl moiety is further substituted; X is O, S, or NR 3 , wherein R 3 is H, C1 to C3 alkyl, halogenated C1 to C3 alkyl, or tert -butyloxycarbonyl; Y is O, S, NR 4 or N(R 4 )R 5 , wherein R 4 and R 5 are independently selected out of H or C1 to C3 alkyl; and wherein if Y is O, S, or NR 4 , then both A are NH, and the punctuated bonds represent a double bond to Y and single bonds to each A; or wherein if Y is N(R 4 )R 5 , then one A is N, the other A is NH, and the punctuated bonds represent a double bond to the A being N, a single bond to the A being NH and a single bond to Y; and use of such a compound in treatment or prevention of an inflammatory disease or an inflammation-related disorder.
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7-(MORPHOLIN-4-YL)PYRAZOLE[1,5-A]PYRIMIDINE DERIVATIVES WHICH ARE USEFUL FOR THE TREATMENT OF IMMUNE OR INFALMMATORY DISEASES OR CANCER (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">A compound of the general formula (I) wherein Y represents —CH<sub>2</sub>— or >C=0; R<sup>1 </sup>is selected from the group consisting of A1, A2 and A3; R<sup>2 </sup>represents dioxothiomorpholino moiety B1, piperazinyl moiety B2, azetidinyl moiety B3, or piperidinyl moiety B4; R<sup>3 </sup>is selected from the group consisting of H, halogen, and C1-C4 alkyl; R<sup>4 </sup>is selected from the group consisting of C1-C4 alkyl, C3-C4-cycloalkyl, C1-C4 alkyl substituted with C1-C4 alkoxy, and CHF<sub>2</sub>, and their pharmaceutically acceptable salts. Pharmaceutical compositions comprising said compounds and their use in the treatment of diseases of immune system, inflammatory diseases and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="240.62mm" wi="56.81mm" file="US20180111939A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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4,6-PYRIMIDINYLENE DERIVATIVES AND USES THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">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, CDKl2, or CDKl3) or a lipid kinase such as a phosphatidylinositol-5-phosphate 4-kinase (PIP4K) (e.g., PI5P4Kα, PI5P4Kβ, or PI5P4Kγ)) in the subject.</p>
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HISTIDYL-TRNA SYNTHETASES FOR TREATING AUTOIMMUNE AND INFLAMMATORY DISEASES (Thu, 26 Apr 2018)
The present invention relates generally to compositions and methods comprising histidyl-tRNA synthetase polypeptides or other specific blocking agents for the treatment autoimmune diseases and other inflammatory diseases, including those related to Jo-1 antibodies.
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TRICYCLIC DERIVATIVE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME (Thu, 26 Apr 2018)
The present invention relates to novel tricyclic derivative compounds, and more specifically to tricyclic derivative compounds, optical isomers thereof, racemates thereof, or pharmaceutically acceptable salts thereof, which have excellent activity against PARP-1, tankyrase-1 or tankyrase-2. The tricyclic derivative compounds, optical isomers thereof, racemates thereof or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, and thus can be effectively used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer.
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HETEROARYL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DISEASES ASSOCIATED WITH PI3 KINASES, CONTAINING SAME AS ACTIVE INGREDIENT (Thu, 26 Apr 2018)
The present invention relates to a heteroaryl derivative or a pharmaceutically acceptable salt thereof, a preparation method therefor, and a pharmaceutical composition for preventing or treating diseases associated with PI3 kinases, containing the same as an active ingredient. The heteroaryl derivative according to the present invention has an excellent effect of selectively inhibiting PI3 kinases, thereby being useful in preventing or treating PI3 kinase diseases such as: cancers such as hematologic malignancy, ovarian cancer, uterine cervical cancer, breast cancer, colorectal cancer, liver cancer, gastric cancer, pancreatic cancer, colon cancer, peritoneal metastatic cancer, skin cancer, bladder cancer, prostate cancer, lung cancer, osteosarcoma, fibrous tumors, and brain tumors; autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosis, multiple sclerosis, diabetes mellitus, hyperthyroidism, myasthenia, Crohn's disease, ankylosing spondylitis, autoimmune pernicious anemia, and Sjogren's syndrome; and respiratory diseases such as chronic obstructive pulmonary disease (COPD), rhinitis, asthma, chronic bronchitis, chronic pulmonary inflammatory diseases, silicosis, pulmonary sarcoidosis, pleurisy, alveolitis, angitis, pneumatosis, pneumonia, and bronchiectasis.
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METHODS FOR THE TREATMENT AND PREVENTION OF INFLAMMATORY DISEASES (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The inventors demonstrate that treatment of young, suckling mice with a glycolipid derived from <i>Helicobacter pylori </i>activates NKT cells in a CD1d-restricted fashion, and is protective against AHR in a model of allergen-induced asthma. The inventors further found that this protective effect can be transferred by NKT cells exposed to the glycolipid, and is associated with the expansion of a suppressive double-negative NKT cells and Foxp3<sup>+</sup> T<sub>Reg </sub>cells. The inventors also demonstrate herein that pretreatment of adult mice with a glycolipid derived from <i>Helicobacter pylori </i>partially suppresses airway hyperreactivity and inhibits BAL inflammation in an ozone-exposure model. Accordingly, provided herein are compositions and methods for the treatment and prevention of inflammatory diseases, such as asthma or autoimmune diseases, in a subject in need thereof.</p>
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A novel compound (KS-513) isolated from Pseudolysimachion rotundum var. subintegrum, the composition comprising the same preventing or treating allergic disease, inflammatory disease, asthma or chronic obstructive pulmonary disease and the use thereof (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">(1aS,1bS,2S,4S,5aR,6S,6aS)-1a-(hydroxymethyl)-4-methoxy-2-(((2S,3R,5S5,6R)-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}, 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) and the use thereof.</p>
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ISOLATED PEPTIDES AND FRAGMENTS THEREOF FROM FIBRINOGEN FOR USE AS DRUGS, PARTICUARLY IN SKIN INFLAMMATORY DISEASES (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">A present invention relates to isolated peptides obtained from human fibrinogen for their use as drug, particularly for the prevention and/or the treatment of inflammatory skin diseases, more particularly acne. The present invention also relates to fragments of these polypeptides, nucleic acid molecules encoding them, expression vectors, host cells, a pharmaceutical composition and a combination product containing them, and their use for treating and/or preventing inflammatory skin diseases, particularly acne.</p>
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INHIBITORS OF PHOSPHOGLYCERATE DEHYDROGENASE (PHGDH) AND USES THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention provides compounds pounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.</p>
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ARYL SULTAM DERIVATIVES AS RORc MODULATORS (Fri, 20 Apr 2018)
<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="33.36mm" wi="69.85mm" file="US20180105516A1-20180419-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, Het, 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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BROMODOMAIN INHIBITORS (Fri, 20 Apr 2018)
Provided are compounds of formula (I),wherein R 1, Y, X 1, X 2, R 2, R 3, R 4, R 5, R 6 and m 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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N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
Provided herein are certain substituted N-aryl and N-heteroaryl piperidine compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1, Q, R5 and R 6 are as defined. The said novel compounds, and pharmaceutically acceptable compositions comprising a compound thereof, may be 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 disease and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
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ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS (Fri, 20 Apr 2018)
In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, L, R4, L1,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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ARYL AND HETEROARYL ETHER DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
Substituted aryl and heteroaryl ether compounds of the Formula (I) and pharmaceutically acceptable salts thereof, wherein X, R 1, R 2, R 3, L, R 4, L 1, Q, and R 5 are as defined herein. These compounds 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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BROMODOMAIN INHIBITORS (Fri, 20 Apr 2018)
Provided herein are compounds of formula (I) wherein R 1, Y, L 1, G 1, X 1, X 2, L 2, R 2, R 3, and R 4 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, which 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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N-ARYL AND N-HETEROARYL PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR BETA AGONISTS, COMPOSITIONS, AND THEIR USE (Fri, 20 Apr 2018)
In its many embodiments, the present invention provides certain substituted N-aryl and N-heteroaryl piperidine compounds of the Formula (I): (Formula (I)) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1,Q, R5 and R6 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, may be 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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INHIBITORS OF ALPHA-AMINO-BETA-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE (Fri, 20 Apr 2018)
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+ 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.
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IMMUNOGLOBULIN SINGLE VARIABLE DOMAIN ANTIBODIES AGAINST OX40L, CONSTRUCTS AND THERAPEUTIC USE (Thu, 19 Apr 2018)
The present invention relates to immunoglobulin single variable domain sequences that are directed against (as defined herein) OX40L, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such immunoglobulin single variable domain sequences. In particular these immunoglobulin single variable domain sequences can block binding of OX40L to OX40. The immunoglobulin single variable domains, compounds and constructs can be used for prophylactic, therapeutic or diagnostic purposes, such as for the treatment of inflammatory disease and/or disorder such as e.g. asthma, allergic asthma, chronic colitis, Crohn's disease, inflammatory bowel disease, and/or arthrosclerosis.
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INHIBITORS OF HISTONE DEACETYLASE (Fri, 13 Apr 2018)
<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="35.64mm" wi="61.72mm" file="US20180099977A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R<sup>2a</sup>, R<sup>2b</sup>, R<sup>2c</sup>, R<sup>5 </sup>and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.</p>
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COMPOUNDS AND COMPOSITIONS FOR TREATING LEISHMANIASIS AND METHODS OF DIAGNOSIS AND TREATING USING SAME (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">Compositions and methods of using these compositions that can include a targeting moiety and a therapeutic agent are described herein. These compositions can be used for treating inflammatory diseases, such as parasitic diseases that result in cutaneous lesions. For example, and without limitation, such an parasitic disease can be leishmaniasis.</p>
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CRYSTAL FORMS OF IMMUNOMODULATORY DRUG POMALIDOMIDE AND CO-CRYSTAL WITH GENTISIC ACID (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">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.</p>
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TRICYCLIC COMPOUND AND JAK INHIBITOR (Fri, 13 Apr 2018)
<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 0 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="113.79mm" wi="58.59mm" file="US20180099966A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BIFUNCTIONAL STAPLED POLYPEPTIDES AND USES THEREOF (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Usesses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.</p>
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COMPOUNDS AND COMPOSITIONS FOR TREATING LEISHMANIASIS AND METHODS OF DIAGNOSIS AND TREATING USING SAME (Fri, 13 Apr 2018)
Compositions and methods of using these compositions that can include a targeting moiety and a therapeutic agent are described herein. These compositions can be used for treating inflammatory diseases, such as parasitic diseases that result in cutaneous lesions. For example, and without limitation, such an parasitic disease can be leishmaniasis.
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TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (Fri, 06 Apr 2018)
<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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RETINOID DERIVATIVES WITH ANTITUMOR ACTIVITY (Fri, 06 Apr 2018)
The present invention relates to compounds of formula (I) and to pharmaceutical compositions containing them, wherein meanings of the substituents are indicated in the description. Such compounds for use in the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, are also within the scope of the present invention.
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SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS (Fri, 06 Apr 2018)
[007801 Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R', R2, R, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.
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RETINOID DERIVATIVES WITH ANTITUMOR ACTIVITY (Thu, 05 Apr 2018)
The present invention relates to new compounds of formula (I) and to pharmaceutical compositions containing them: The use of such compounds for the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, is also within the scope of the present invention.
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NEW COMPOUNDS FOR TREATING CANCER AND OTHER DISEASES (Thu, 05 Apr 2018)
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.
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BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS (Fri, 30 Mar 2018)
The present application provides the compounds of formula I or pharmaceutically acceptable salts, isomers, tautomer, or a mixture thereof, wherein t, R1, R2, R3, R4, and R6 are as described herein. The compounds of formula I selectively inhibit the activities of PI3K isoforms and are useful in therapeutic treatments, in particular in the treatment of inflammatory diseases and cancer.
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NOVEL AMINO PYRIMIDINE DERIVATIVES (Thu, 29 Mar 2018)
The present invention describes new amino pyrimidine derivatives and pharmaceutically acceptable salts thereof which appear to interact with Bruton's tyrosine kinase (Btk). Accordingly, the novel amino pyrimidines may be effective in the treatment of autoimmune disorders, inflammatory diseases, allergic diseases, airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), transplant rejection, cancers e.g. of hematopoietic origin or solid tumors.
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NOVEL COMPOUND USEFUL FOR THE TREATEMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">A pyrazolopyridine compound according to Formula I, able to inhibit JAK is disclosed, as well as pharmaceutically acceptable salts, a solvate thereof, solvates of the pharmaceutically acceptable salts and biologically active metabolites thereof. The compound may be prepared as a pharmaceutical composition, and may be used for the treatment or prophylaxis of a variety of conditions in mammals including humans, and particularly, such conditions as may be associated with aberrant JAK activity, including by way of non-limiting example, allergy, inflammatory conditions, autoimmune diseases, proliferative diseases, transplant rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="53.93mm" wi="69.85mm" file="US20180078547A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CYCLIC COMPOUND (Thu, 22 Mar 2018)
The present invention provides compounds having a Toll-like receptor 4 (TLR4) signaling inhibitory action useful as preventive and therapeutic drugs of autoimmune disease and/or inflammatory 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: (wherein, each symbol is explained in greater detail in the specification).
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PYRIDAZINE DERIVATIVES AS RORc MODULATORS (Fri, 16 Mar 2018)
<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="41.83mm" wi="69.85mm" file="US20180072683A1-20180315-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">or pharmaceutical salts thereof,</li> <li id="ul0002-0002" num="0000">wherein m, A, X, Y, Z, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5</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.</li> </ul> </li> </ul> </p>
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INHIBITORS OF HISTONE DEACETYLASE (Fri, 16 Mar 2018)
<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="35.48mm" wi="64.18mm" file="US20180072671A1-20180315-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X<sub>1</sub>, X<sub>2</sub>, X<sub>3</sub>, X<sub>4</sub>, X<sub>5</sub>, W<sub>1</sub>, W<sub>2</sub>, W<sub>3</sub>, and W<sub>4 </sub>are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting β-cells and improving insulin resistence. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals.</p>
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Fumarate Analogs and Uses Thereof (Fri, 16 Mar 2018)
<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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USE OF RECOMBINANT LYMPHOCYTE ACTIVATION GENE-3 (Fri, 16 Mar 2018)
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 of 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.
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SITE SPECIFIC CURCUMIN-POLYMER MOLECULAR COMPLEXES AND METHODS OF TREATING COLON DISEASES AND INFLAMMATION (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">Methods and materials relating to a medicament preparation comprising a curcuminoid component, such as curcumin, and a polymer component having a backbone comprising polymethacrylate or methyl methacrylate provided as a curcuminoid-polymer complex, which enhances the solubility, stability and bioavailability of the curcumin component and are useful for the treatment of various inflammatory diseases and conditions when delivered to the gastro-intestinal tract, including sepsis, mucositis, gastritis, infections, inflammatory bowel disease and cancers of GIT. The curcumin-polymer complex inhibiting the activation of TLR receptors and thereby reduce the release of inflammatory cytokines, such that the curcumin-polymer complexes are more potent than free curcumin in antagonizing on the activation of TLR4.</p>
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IMIDAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF AUTOIMMUNE OR INFLAMMATORY DISEASES OR CANCERS (Fri, 09 Mar 2018)
Compounds of formula (I) and salts thereof: Formula (I) wherein R1, R2, R3 and a are as defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain containing proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.
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IMIDAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF AUTOIMMUNE OR INFLAMMATORY DISEASES OR CANCERS (Fri, 09 Mar 2018)
Compounds of formula (I) and salts thereof: wherein R1, R2, R3, a, X1, X2, X3, X4, and X5 are as defined hereinbefore. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain containing proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.
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Purinone compounds as kinase inhibitors (Fri, 09 Mar 2018)
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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1-Amino-triazolo(1,5-A)pyridine-substituted Urea Derivative and Uses Thereof (Fri, 02 Mar 2018)
<p id="p-0001" num="0000">Provided herein is a compound, 1-(4-(3-amino-[1,2,3]triazolo[1,5-a]pyridin-4-yl)phenyl)-3-(3-chlorophenyl)urea, pharmaceutical compositions thereof and crystal forms thereof. Also provided are particles (e.g., nanoparticles) comprising the compound, and pharmaceutical compositions thereof that are mucus penetrating. Also provided herein are methods and kits for using the compound, 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>
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LANTHIONINE SYNTHETASE C-LIKE 2-BASED THERAPEUTICS (Fri, 02 Mar 2018)
<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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PRODRUGS ACTIVATED BY REACTIVE OXYGEN SPECIES FOR USE IN THE TREATMENT OF INFLAMMATORY DISEASES AND CANCER (Fri, 02 Mar 2018)
Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method for preparing said prodrugs.
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PRODRUGS ACTIVATED BY REACTIVE OXYGEN SPECIES FOR USE IN THE TREATMENT OF INFLAMMATORY DISEASES AND CANCER (Fri, 02 Mar 2018)
Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method for preparing said prodrugs.
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NOVEL HETEROCYCLIC COMPOUNDS AND USE THEREOF IN MEDICINE AND IN COSMETICS (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">The invention relates to novel heterocyclic compounds of general formula (I), as well as their pharmaceutically acceptable salts, and their enantiomers. The invention also relates to the use thereof as a medicinal product, preferably in the prevention and/or treatment of inflammatory diseases with a neurogenic component or use thereof as a cosmetic. The compounds of the present invention act as antagonists of the CGRP-R receptor.</p>
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Derivatives of 1-[(cyclopentyl or 2-pyrrolidinyl)carbonylaminomethyl]-4-(1,3-Thiazol-5-yl) benzene which are Useful for the Treatment of Proliferative, Autoimmune or Inflammatory Diseases (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, having utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for the preparation thereof, and use in medicine. There is particularly provided PROTACs which bind to a protein within the bromo- and Extra-terminal (BET) family of proteins, and especially to PROTACs including novel small molecule E3 ubiquitin ligase protein binding ligand compounds which selectively induce degradation of the BRD4 protein within the bromodomain of the BET family of proteins.</p>
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Pyridazine derivatives as RORc modulators (Fri, 23 Feb 2018)
<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="33.44mm" wi="69.85mm" file="US09994551-20180612-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or pharmaceutical salts thereof, <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<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </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.</li> </ul> </li> </ul> </p>
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Lactone intermediates of nicotinamide riboside and nicotinate riboside (Thu, 22 Feb 2018)
A compound of formula I or IA: wherein R1 is an optional substituent; n is 0-4; R2 and R3 are selected from hydrogen and a substituent, or R2 and R3 join together to form an optional substituted ring; X is an anion. The compounds of formula I or IA can be reduced or decyclised to form nicotinamide ribosides or nicotinate ribosides and thus offer a new route to these compounds (see claim 1 for a new route to a compound of formula V or VA from a compound of formula I or IA). In another aspect, the compound of formula I or IA find use in the treatment of aging, stress, cardiovascular disease, cell death, cancer, metabolic disorder, neuronal disease, blood coagulation disorder, weight control, inflammatory disease, flushing, viral infection, fungal infection, dietary deficiency of vitamin B3, pellagra, pellagra-like condition, vitamin B3 deficiency, or a mitochondrial disease or disorder.
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BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">Compounds of formula (I) and salts thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.89mm" wi="69.85mm" file="US20180044317A1-20180215-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4 </sub>are defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.</p>
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KINASE INHIBITORS (Fri, 16 Feb 2018)
<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="48.60mm" wi="76.03mm" file="US20180044288A1-20180215-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1A </sup>to R<sup>1E</sup>, R<sup>2 </sup>to R<sup>5</sup>, L and X<sup>1 </sup>to X<sup>3 </sup>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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Pyridinone and pyridazinone derivatives (Fri, 16 Feb 2018)
The present invention provides for compounds of formula (I) wherein J is a group of formula Ha or Ilb: A1 , A2 , A', A4 , J, and X3 have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, diabetes, obesity, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula I.
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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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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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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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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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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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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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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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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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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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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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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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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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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 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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Pyrazole P38 map kinase inhibitors (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="US10000471-20180619-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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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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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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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(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-[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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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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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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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="US09902725-20180227-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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 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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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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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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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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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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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="US10017492-20180710-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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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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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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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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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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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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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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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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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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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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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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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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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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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Beta 2-AR exciting and anti-inflammatory dual-function alkaloid and application thereof (Wed, 16 Aug 2017)
The invention discloses alkaloid as shown in the formula I or II and an analogue, an isomer, a despinner or a derivative thereof, and the the formula I or II is shown in the specification. The compound is separated from purslane, and a research shows that the compound has beta 2-AR exciting and anti-inflammatory dual-function activity; an available compound is provided for treatment of respiratory system diseases such as asthma and relevant inflammatory diseases.
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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 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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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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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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A kind of a substituted quinazoline-4-ketone compound and a preparation method and medical application thereof (Wed, 02 Aug 2017)
The invention relates to a new PI3K[delta] inhibitor compound shown as the general formula I and having a substituted quinazoline-4-ketone structure, a preparation method of the compound, and an application of the compound to prepare a medicine for preventing and/or treating PI3K[delta]-related diseases, which include tumor and inflammatory diseases.
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Bromine structural-domain inhibitor (Sat, 29 Jul 2017)
The invention relates to a bromine structural-domain inhibitor, provides a compound shown as a formula (I) and pharmaceutically acceptable salt of the compound and further provides a medicine composition with the compound shown in the formula (I) or a plurality of compounds shown in the formula (I). An A<1>, an A<2>, an A<3>, an A<4>, an X<1>, an X<2>, a Y<1>, an L<1>, a G<1>, an R<x> and an R<y> have values defined in optional instruction books. The compound can be used as a preparation for treating diseases and disease states including inflammatory diseases, cancer and AIDS (acquired immune deficiency syndrome).
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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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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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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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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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Prenylated flavonoid, and applications thereof in preparing drugs used for treating inflammatory diseases (Wed, 05 Jul 2017)
The invention relates to a prenylated flavonoid, and applications thereof in preparing drugs used for treating inflammatory diseases. The prenylated flavonoid is a novel compound separated from artocarpus heterophyllus of Artocarpus, Moraceae, and is named as artoheteroid C. The structure of artoheteroid C is disclosed in the invention, possesses high inhibition activity on mouse neutrophil respiratory burst, can be used for preparing drugs used for treating inflammatory diseases, and can be used for clinical treatment of oxidative damages, such as rheumatoid arthritis, compensatory anti-inflammatory response syndrome, and systemic inflammatory response syndrome, caused by neutrophil excessive activation; and the IC50 value is 7.5<mu>M.
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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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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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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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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="30.56mm" wi="72.56mm" file="US09943521-20180417-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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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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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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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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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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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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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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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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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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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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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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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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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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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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 (<i>e.g</i>., 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, <i>e.g</i>., 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, <i>e.g</i>., 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, <i>e.g</i>., reduces, deactivates, or inhibits GITR and/or 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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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 (Thu, 25 May 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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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="60.20mm" file="US10004716-20180626-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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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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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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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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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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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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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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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Dendrimer 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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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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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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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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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 R<sp>1</sp>, R<sp>2</sp>, 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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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 (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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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 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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Bet-protein inhibiting 3,4-dihydropyrido[2,3-b]pyrazinones with meta-substituted aromatic amino- or ether groups (Thu, 20 Apr 2017)
The invention relates to BET-protein-inhibiting, in particular BRD4-inhibiting 3,4-dihydropyrido[2,3-b]pyrazinones with meta-substituted aromatic amino or ether groups of general formula (I), in which A, X, Y, R1, R2, R3, R4, R5, R6, and n have the meanings indicated in the description, pharmaceutical agents containing the claimed compounds, and the prophylactic and therapeutic use of said pharmaceutical agents in the case of hyperproliferative diseases, in particular in the case of tumor diseases. The invention further relates to the use of BET protein inhibitors in the case of viral infections, neurodegenerative diseases, inflammatory diseases, and atherosclerotic diseases and in male fertility control.
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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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