PATENTSCOPE: EN_ALL:nmr AND PA:pfizer
CRYSTALLINE FORM OF LORLATINIB FREE BASE HYDRATE (Fri, 19 Apr 2019)This invention relates to a crystalline form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl- 15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclo- tetradecine-3-carbonitrile (lorlatinib) free base hydrate (Form 24). This invention also relates to pharmaceutical compositions comprising Form 24, and to methods of using Form 24 and such compositions in the treatment of abnormal cell growth, such as cancer, in a mammal.
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REAGENTS FOR FLUOROSULFATING ALCOHOLS OR AMINES (Fri, 22 Feb 2019)
Disclosed herein are compounds of formula Ar-N(SO2F)2, wherein Ar is selected from an optionally substituted aryl, an optionally substituted five-membered heteroaryl, or an optionally substituted six-membered heteroaryl. Also disclosed are methods of synthesizing the above compounds by reacting a compound of formula Ar-NH-R9 with MN(SO2F)2.
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PYRAZOLO[1,5-A]PYRAZIN-4-YL AND RELATED DERIVATIVES (Fri, 22 Feb 2019)
A compound having the structure: (I) or (II) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein variables are defined in the specification. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.
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DIHYDRO-PYRROLO-PYRIDINE DERIVATIVES (Fri, 28 Dec 2018)
The present invention provides, in part, compounds of Formula I, or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N- oxide, wherein: (R1)a, (R2)b, (R3)c, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4- associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.
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ANTI-ROBO2 ANTIBODIES, COMPOSITIONS, METHODS AND USES THEREOF (Fri, 14 Dec 2018)
The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to ROBO2, as well as uses, and methods thereof.
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OLIGONUCLEOTIDE COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 07 Dec 2018)
Among other things, the present disclosure provides designed APOC3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.
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OLIGONUCLEOTIDE COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 07 Dec 2018)
Among other things, the present disclosure provides designed PNPLA3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.
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NOVEL IMIDAZO[4,5-C]QUINOLINE DERIVATIVES AS LRRK2 INHIBITORS (Fri, 14 Sep 2018)
The present invention provides novel imidazo[4,5-c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof I wherein R1, R2 and R3 are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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CYCLIC SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE DERIVATIVES (Fri, 14 Sep 2018)
The present invention provides novel cyclic substituted imidazo[4,5- c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof, wherein R1, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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LARGE SCALE PRODUCTION PROCESS FOR CAPPED AND UN-CAPPED ANTIBODY CYSTEINES AND THEIR USE IN THERAPEUTIC PROTEIN CONJUGATION (Fri, 17 Aug 2018)
Optimizing production of selectively capped, and uncapped, cysteines on antibodies by manipulation of cell growth conditions including the deliberate depletion of cysteine and/or cystine in the cell culture process by way of media components, batch duration, or cell density to achieve efficient production of proteins including antibody-drug-conjugates (ADCs).; conjugating a TNB-capped cysteine-containing protein by reacting it with a reducing agent capable of detaching the TNB-capping moieties from the protein without significantly reducing antibody inter-chain sulfur bonds, and conjugating reduced sulfur bonds on the protein to a payload through a reactive linking moiety.
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CALICHEAMICIN DERIVATIVES AND ANTIBODY DRUG CONJUGATES THEREOF (Fri, 03 Aug 2018)
The present invention is directed to novel calicheamicin derivatives useful as payloads in antibody-drug-conjugates (ADC's), and to payload-linker compounds and ADC compounds comprising the same; to pharmaceutical compositions comprising the same and to methods for using the same to treat pathological conditions such as cancer.
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IMMUNOGENIC COMPOSITIONS FOR USE IN PNEUMOCOCCAL VACCINES (Fri, 27 Jul 2018)
An object of the present invention is to provide immunogenic compositions for protection against S. pneumoniae, in particular against S. pneumoniae serogroup 18, while limiting the number of conjugates. The present invention therefore relates to new immunogenic compositions for use in pneumococcal vaccines and to vaccination of human subjects, in particular infants and elderly, against pneumoccocal infections using said immunogenic compositions.
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1,1,1-TRIFLUORO-3-HYDROXYPROPAN-2-YL CARBAMATE DERIVATIVES AS MAGL INHIBITORS (Fri, 27 Jul 2018)
The present invention provides, in part, compounds of Formula (I) and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
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HETEROCYCLIC SPIRO COMPOUNDS AS MAGL INHIBITORS (Fri, 27 Jul 2018)
The present invention provides, in part, heterocyclic spiro compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.
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GLP-1 RECEPTOR AGONISTS AND USES THEREOF (Fri, 22 Jun 2018)
Provided herein are 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, 7-aza- and 4,7-diaza-benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.
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HETEROARYLPHENOXY BENZAMIDE KAPPA OPIOID LIGANDS (Fri, 01 Jun 2018)
The present invention provides compounds of Formula I: and pharmaceutically acceptable salts thereof wherein the variables R1, R2, R3, R4, R9, X, m and n are as defined herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compound s or s al ts, an d thei r uses for treating kappa opioid (κ-opioid) associated disorders including, e.g., a neurological disorder, or psychiatric disorder such as a neurocognitive disorder, substance abuse disorder, depressive disorder, anxiety disorder, trauma and stressor related disorder and feeding and eating disorder.
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IMMUNOGENIC POLYSACCHARIDE PROTEIN CONJUGATED COMPRISING A POLYSACCHARIDE DERIVED FROM B STREPTOCOCCUS GBS (Fri, 18 May 2018)
The invention relates to immunogenic compositions comprising a capsular polysaccharide (CP) from Streptococcus agalactiae, commonly referred to as group B streptococcus (GBS), conjugated to a carrier protein, and optionally including an aluminum-based adjuvant. The invention further relates to methods for inducing an immune response in subjects against GBS and/or for reducing or preventing invasive GBS disease in subjects using the compositions disclosed herein. The resulting antibodies can be used to treat or prevent GBS infection via passive immunotherapy.
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DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS (Fri, 23 Feb 2018)
Compounds of Formula (I) that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.
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PYRIDOPYRIMDINONE CDK2/4/6 INHIBITORS (Fri, 23 Feb 2018)
This invention relates to compounds of general Formula (I), and pharmaceutically acceptable salts thereof, in which R1, R2, R2A, R2B, R3, R4, R5A, R5B, R6, R7, R8, R9, p, q and r are as defined herein, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.
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HETEROARYL SULFONE-BASED CONJUGATION HANDLES, METHODS FOR THEIR PREPARATION, AND THEIR USE IN SYNTHESIZING ANTIBODY DRUG CONJUGATES (Fri, 09 Feb 2018)
The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R1, R2, Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drig conjugates, and the resulting antibody drig conjugates made with components having heteroaryl sulfone- based conjugation handles.
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