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 inhibitor with good cellular activity (IC(50)=1.1 microM) against T-cell proliferation.