Synthesis and Identification of a new class of antileukemic agents containing 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole

Recently we have reported the effect of (S)-6-aryl urea/thiourea substituted-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazole derivatives as potent anti-leukemic agents. To elucidate further the Structure Activity Relationship (SAR) studies on the anti-leukemic activity of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazole moiety, a series of 2-arlycarboxamide substituted–(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole were designed, synthesized and evaluated for their anti-leukemic activity by trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) assays and cell cycle analysis. Results suggest that the position, number and bulkiness of the substituent on the phenyl ring of aryl carboxamide moiety at 2nd position of 6-amino-4,5,6,7-tetrhydrobenzo[d]thiazole play a key role in inhibiting the proliferation of leukemia cells. Compounds with ortho substitution showed poor activity and with meta and para substitution showed good activity.

A series of novel 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzothiazole derivatives 4(a–h) were synthesized and evaluated for their efficacy as anti-leukemic agents. Compound 4e with bulky tert-buty group at para position showed more potent activity.Figure optionsDownload as PowerPoint slide