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

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 inh...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2003-07, Vol.13 (13), p.2145-2149
Hauptverfasser:	Das, Jagabandhu, Lin, James, Moquin, Robert V, Shen, Zhongqi, Spergel, Steven H, Wityak, John, Doweyko, Arthur M, DeFex, Henry F, Fang, Qiong, Pang, Suhong, Pitt, Sidney, Shen, Ding Ren, Schieven, Gary L, Barrish, Joel C
Format:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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.
ISSN:	0960-894X
DOI:	10.1016/S0960-894X(03)00380-9