Atsu Apedo

CCDC 2119841: Experimental Crystal Structure Determination

Elizabeth A. Jurica, Ximao Wu, Kristin N. Williams, Lauren Haque et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities

Elizabeth A. Jurica, Ximao Wu, Kristin N. Williams, Lauren Haque et autres

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Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA 1 ) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases

Peter T. W. Cheng, Robert F. Kaltenbach, Hao Zhang, Jun Shi et autres

The oxycyclohexyl acid BMS-986278 ( 33 ) is a potent lysophosphatidic acid receptor 1 (LPA 1 ) antagonist, with a human LPA 1 K b of 6.9 nM. The structure–activity relationship (SAR) studies starting from the LPA 1 antagonist clinical compound BMS-986020 …

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CCDC 2096775: Experimental Crystal Structure Determination

Huji Turdi, Hannguang J. Chao, Jon J. Hangeland, Saleem Ahmad et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Screening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders

Huji Turdi, Hannguang J. Chao, Jon J. Hangeland, Saleem Ahmad et autres

MGAT2 inhibition is a potential therapeutic approach for the treatment of metabolic disorders. High-throughput screening of the BMS internal compound collection identified the aryl dihydropyridinone compound 1 (hMGAT2 IC 50 = 175 nM) as a hit. Compound 1 had moderate potency against …

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Online LC–GC: The Ultimate “GC Connection”

Nicholas H. Snow, Atsu Apedo

Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists

Jun Shi, Zhengxiang Gu, Elizabeth A. Jurica, Ximao Wu et autres

G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism …

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CCDC 1568523: Experimental Crystal Structure Determination

Donald Pinto, Michael J. Orwat, Leon M. Smith, Mimi L. Quan et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

CCDC 1559162: Experimental Crystal Structure Determination

Jun Shi, Zhengxiang Gu, Elizabeth A. Jurica, Ximao Wu et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212)

Donald Pinto, Michael J. Orwat, Leon M. Smith, Mimi L. Quan et autres

Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to …

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Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3′-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor

Xiang‐Yang Ye, Stephanie Chen, Shung Wu, David Yoon et autres

BMS-816336 ( 6n-2 ), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC 50 3.0 nM) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 6n-2 exhibits a robust …

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Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode

Elizabeth A. Jurica, Ximao Wu, Kristin N. Williams, Andrés S. Hernández et autres

A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4- cis -CF …

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