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Your search keyword '"ChiehYing J. Chang"' showing total 3 results
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3 results on '"ChiehYing J. Chang"'

1. Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)

Author

Tracy L. Taylor, Douglas G. Batt, Lorell Discenza, ChiehYing J. Chang, Luisa Salter-Cid, Kim W. McIntyre, Myra Beaudoin Bertrand, Percy H. Carter, Yingru Zhang, Qingjie Liu, James R. Burke, Andrew J. Tebben, Zheng Yang, Joel C. Barrish, Rick Rampulla, Aberra Fura, Daniel W. Kukral, Joseph A. Tino, Punit Marathe, Huiping Zhang, Jun Dai, Qing Shi, Arvind Mathur, Kathleen M. Gillooly, Mark A. Pattoli, Mary T. Obermeier, Stacey Skala, Jodi K. Muckelbauer, George V. De Lucca, Rodney Vickery, and Celia D’Arienzo

Subjects
0301 basic medicine, medicine.drug_class, Stereochemistry, Carbazoles, Administration, Oral, Biological Availability, Carboxamide, Crystallography, X-Ray, Permeability, Cell Line, Arthritis, Rheumatoid, 03 medical and health sciences, chemistry.chemical_compound, Mice, Structure-Activity Relationship, 0302 clinical medicine, Dogs, In vivo, Drug Discovery, medicine, Agammaglobulinaemia Tyrosine Kinase, Bruton's tyrosine kinase, Structure–activity relationship, Animals, Humans, Quinazolinones, biology, Carbazole, Protein-Tyrosine Kinases, Small molecule, Arthritis, Experimental, Macaca fascicularis, 030104 developmental biology, chemistry, Cell culture, 030220 oncology & carcinogenesis, Antirheumatic Agents, biology.protein, Microsomes, Liver, Molecular Medicine, Tyrosine kinase
Abstract

Bruton’s tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure–activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.

Published
2016

2. De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold

Author

Dawn K. Stetsko, Dominique Besse, Francois Caussade, Eric Nicolai, Brett R. Beno, Stacey Skala, Michele Launay, Dominique Potin, ChiehYing J. Chang, Suzanne J. Suchard, Patrice Malabre, Edwin J. Iwanowicz, Maud Fabreguette, Gordon Todderud, Daniel L. Cheney, Steven Sheriff, Joel C. Barrish, T. G. Murali Dhar, and Diane Hollenbaugh

Subjects
Scaffold, Endothelium, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, Hydantoin, chemical and pharmacologic phenomena, Biochemistry, Inhibitory Concentration 50, Structure-Activity Relationship, chemistry.chemical_compound, Drug Discovery, medicine, Humans, Beta (finance), Molecular Biology, Inflammation, Bicyclic molecule, Hydantoins, Organic Chemistry, hemic and immune systems, Adhesion, Bridged Bicyclo Compounds, Heterocyclic, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1, In vitro, Cell biology, medicine.anatomical_structure, chemistry, Design synthesis, Drug Design, Molecular Medicine, HeLa Cells, Protein Binding
Abstract

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Published
2005
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3. Design of LFA-1 antagonists based on a 2,3-dihydro-1H-pyrrolizin-5(7aH)-one scaffold

Author

ChiehYing J. Chang, T. G. Murali Dhar, Michael A. Poss, Joel C. Barrish, Dawn K. Stetsko, Linda M. Phillips, Yingru Zhang, Michele Launay, Murray McKinnon, Dominique Potin, Suzanne J. Suchard, Wayne Vaccaro, Steven Sheriff, and Dharmpal S. Dodd

Subjects
Scaffold, Stereochemistry, Chemistry, Pharmaceutical, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, Stereoisomerism, Crystallography, X-Ray, Biochemistry, Chemical synthesis, Inhibitory Concentration 50, Drug Discovery, Humans, Pyrroles, Lymphocyte function-associated antigen 1, Cell adhesion, Molecular Biology, Chemistry, Cell adhesion molecule, X-Rays, Organic Chemistry, Temperature, Biological activity, In vitro, Lymphocyte Function-Associated Antigen-1, Models, Chemical, Drug Design, Molecular Medicine, Drug Screening Assays, Antitumor, HeLa Cells
Abstract

A new class of lymphocyte function-associated antigen-1 (LFA-1) antagonists is described. Elaboration of the 2,3-dihydro-1H-pyrrolizin-5(7aH)-one scaffold resulted in the synthesis of potent inhibitors of the LFA-1/ICAM-1 interaction. Along with the in vitro activity, we present the X-ray crystal structure of the complex of compound 9b, in a novel binding mode to the I-domain of LFA-1.

Published
2006

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