Bristol-myers Squibb Compnay

Amira Pharmaceuticals, Inc.

Innate Tumor Immunity, Inc.

Victor W Rosso

John J Venit

Jun Li

Chenkou Wei

Qi Gao

Michael J Orwat

Robert J Cherney

Percy H Carter

Thomas Jon Seiders

Gretchen M Schroeder

Jingyang Zhu

Bin Zheng

Michael J Smith

Jason Edward Brittain

Steven R Fabian

Ke Chen

Mary F Malley

Gary D Madding

Jason G Chen

Sergei Kolotuchin

Jianji Wang

Ambarish K Singh

Dilbir S Bindra

Waldemar Ruediger

Michael E Randazzo

Adrian Ortiz

Ajit B Thakur

Eric M Simmons

Christopher David King

Gerald L Powers

Harold Norris Weller, Iii

Atul S Kotnis

Amanda J Rogers

Sha Lou

Neil A Strotman

Joseph Nolfo

Erik A Rubin

Joerg Deerberg

D David Hennings

Tamas Benkovics

Daniel S Treitler

Raymond E Weaver

A Erik Rubin

Alexander Bertok

Christopher Robert Jamison

Roxana Schlam

Maxime C D Soumeillant

Robert P Discordia

Bing-Shiou Yang

Dong Lin

Cletus John Nunes

Madhushree Yeshwant Gokhale

Bahar Inankur

Michael Dummeldinger

Francis J Okuniewicz

Maxine Soumellant

Peter Lee

Mayra B Reyes

Mansi S Shah

Walter Ruediger

Imre M Vit Z

Glen Young

Susanne Kiau

Steven Tymonko

Sergei V Kolotuchin

Disclosed is crystalline Form E of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d)pyridazine-3-carboxamide. Form E is a neat crystalline form. Characterization data for Form E are disclosed.

Crystal form of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d) pyridazine-3-carboxamide

Improved methods and intermediates thereof for preparing substituted 4-amino-1H-imidazo[4,5-c]quinoline compounds are described. These compounds are useful as NLRP3 modulators.

Substituted 4-amino-1H-imidazo[4,5-c]quinoline compounds and improved methods for their preparation

The invention relates to an improved process for synthesizing 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide of the formula: [INSERT CHEMICAL STRUCTURE HERE] Compound I is currently in clinical trials for the treatment of auto-immune and auto-inflammatory diseases such as psoriasis. 

Process for the preparation of 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide

Described herein is the LPA1 antagonist 1-{4'-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid (Compound 1), or pharmaceutically acceptable salts thereof. Also described are methods of preparing the LPA1 antagonist, or pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions suitable for administration to a mammal that include the LPA1 antagonist, or pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating LPA-dependent or LPA-mediated diseases or conditions.

Polycyclic LPA1 antagonist and uses thereof

Novel [1,2,4]triazolo[1,5-]pyridinyl-6-yl-substituted tetrahydroisoquinolines are described in the present invention. These compounds and crystalline forms SA1 and N-2 are used in the treatment of various neurological and physiological disorders. Methods of making these compounds and crystalline forms SA-1 and N-2 are also described in the present invention.

Crystalline forms of (S)-7-([1,2,4]triazolo[1,5-a ]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline and use thereof

Novel [1,2,4]triazolo[1,5-a]pyridinyl-6-yl-substituted tetrahydroisoquinolines are described in the present invention. These compounds and crystalline forms SA1 and N-2 are used in the treatment of various neurological and physiological disorders. Methods of making these compounds and crystalline forms SA-1 and N-2 are also described in the present invention.

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The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

Provided is a dynamic resolution method of enriching a desired isomer of an alpha-substituted carboxylic acid relative to an undesired isomer, the method comprising: (a) in a solvent, contacting the alpha-substituted carboxylic acid, wherein the alpha substitution is with a leaving group and wherein the alpha carbon is chiral, with a homochiral amine to form a salt that is partially insoluble under selected reaction conditions, wherein the homochiral amine is selected so that the solubility of the amine salt of the undesired alpha-substituted carboxylic acid is greater than that of the amine salt of the desired alpha-substituted carboxylic acid under the selected reaction conditions; (b) reacting under the selected reaction conditions the salt with a nucleophile, wherein the reacting is effective in producing a net increase in the less soluble amine salt of the alpha-substituted carboxylic acid, and wherein the selected conditions are selected to (i) promote nucleophilic substitution of the nucleophile and the leaving group or (ii) to produce the increase in the less soluble amine salt in the absence of a strong base; and (c) maintaining the reaction for a period of time effective to increase the amount of the desired alpha-substituted carboxylic acid isomer.

Dynamic resolution of isomers and resolved isomers

The instant invention provides crystalline forms of 3-(1-hydroxy-1-methyl-ethyl)-1-(4-methoxy-phenyl)-6-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one and its solvates thereof; processes for the production of such crystalline forms; pharmaceutical compositions comprising such crystalline forms; and methods of treating thromboembolic disorders with such crystalline forms or such pharmaceutical compositions.

Crystalline forms of a factor Xa inhibitor

Multiple samples are prepared in slurry form and deposited through a funnel plate by a multiprobe liquid handler into an array of inserts situated in openings in a housing. Each insert has a recess that extends through the insert body and a filter disc situated in the recess to support the sample. The filter is held in place by an annular part which defines a channel providing access to the filter through the lower portion of the recess. A pressure differential is created across each of the filters by attaching a vacuum manifold to the bottom of the housing to simultaneously remove the liquid from each of the samples, leaving the samples in powder form. The housing is then placed in the X-ray diffractometer for sequential analysis of each of the samples, while the samples are situated in the inserts.

High throughput X-ray diffraction filter sample holder

The base of the modular reactor includes a frame which defines an opening into which one of a plurality of interchangeable reaction vessel carrying inserts can be removeably received. Each insert has an array of recesses adapted to receive a different number of reaction vessels of different sizes. The recesses are positioned such that all arrays are suitable for use with a standard automated liquid handier. The frame has fluid flow channels for regulating the temperature of the lower portions of the vessels. A temperature control module can be received over the base to regulate the temperature of the upper portions of the vessels for reflux reactions. The corner radii of the insert and frame opening cooperate to permit the insert to be received in the frame in only one orientation. The walls of the insert are inclined to facilitate removal by a friction fit tool. Each vessel receiving recess has a self-centering conical or semi-circular shaped bottom to maximize heat transfer and distribute the load uniformly. The vessels seat as close to the bottom surface of the base as possible to facilitate use with an air driven magnetic stirrer. A thin, electrically heated plate may be received between the base and the stirrer.

Parallel chemistry reactor with interchangeable vessel carrying inserts

Multiple parallel chemical reactions are performed under pressure in a reactor including a multi-row array of reaction vessels situated between a temperature control base and a fluid flow manifold. The manifold consists of an input portion connected to the fluid supply by a five-way valve and a distribution portion which includes separate parallel distribution channels, one for each row of reaction vessels. A control valve for each distribution channel is interposed between the manifold portions such that the fluid flow to each row of reaction vessels can be independently controlled. An explosion proof transparent shield can be situated between the base and manifold, surrounding the reaction vessels. The interior of the shield can be flooded with inert gas.

High pressure chemistry reactor

Novel reaction conditions for the cleavage of silyl ethers from silyl protected taxane precursors to afford paclitaxel and paclitaxel analogues in high yield and quality are described. Paclitaxel is prepared from a taxane precursor by treating the taxane precursor with a strong acid such as trifluoroacetic acid in a solvent such as aqueous acetic acid, such that the amount and number of side reactions and taxane impurities are significantly minimized. Also desribed are the crystallization methods for the isolation of paclitaxel in either of the two crystal forms A or B. Paclitaxel and paclitaxel analogues are anti-cancer agents.

Reaction conditions for the cleavage of silyl ethers in the preparation of paclitaxel(taxol&reg;) and paclitaxel analogues

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East Windsor, NJ, United States of America

Victor W Rosso