Molecular design, synthesis, and structure-Activity relationships leading to the potent and selective p56(lck) inhibitor BMS-243117

Jagabandhu Das; James Lin; Robert V Moquin; Zhongqi Shen; Steven H Spergel; John Wityak; Arthur M Doweyko; Henry F DeFex; Qiong Fang; Suhong Pang; Sidney Pitt; Ding Ren Shen; Gary L Schieven; Joel C Barrish

doi:10.1016/s0960-894x(03)00380-9

Molecular design, synthesis, and structure-Activity relationships leading to the potent and selective p56(lck) inhibitor BMS-243117

Bioorg Med Chem Lett. 2003 Jul 7;13(13):2145-9. doi: 10.1016/s0960-894x(03)00380-9.

Authors

Jagabandhu Das¹, James Lin, Robert V Moquin, Zhongqi Shen, Steven H Spergel, John Wityak, Arthur M Doweyko, Henry F DeFex, Qiong Fang, Suhong Pang, Sidney Pitt, Ding Ren Shen, Gary L Schieven, Joel C Barrish

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, 08543-4000, Princeton, NJ, USA. jagabandhu.das@bms.com

PMID: 12798323
DOI: 10.1016/s0960-894x(03)00380-9

Abstract

A series of structurally novel benzothiazole based small molecule inhibitors of p56(lck) were prepared to elucidate their structure-activity relationships (SARs), selectivity and cell activity in the T-cell proliferation assay. BMS-243117 (compound 2) is identified as a potent, and selective Lck inhibitor with good cellular activity (IC(50)=1.1 microM) against T-cell proliferation.

MeSH terms

Adenosine Triphosphate / metabolism
Binding Sites / drug effects
Cell Division / drug effects
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Humans
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
Models, Molecular
Molecular Conformation
Structure-Activity Relationship
Substrate Specificity
T-Lymphocytes / drug effects
Thiazoles / chemical synthesis*
Thiazoles / pharmacology*
Urea / chemistry

Substances

BMS-243117
Enzyme Inhibitors
Thiazoles
Adenosine Triphosphate
Urea
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)