ABL kinase inhibitory and antiproliferative activity of novel picolinamide based benzothiazoles

作者：El Damasy Ashraf Kareem; Cho Nam Chul; Kang Soon Bang; Pae Ae Nim; Keum Gyochang^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(10): 2162-2168.

DOI：10.1016/j.bmcl.2015.03.067

• Chronic myelogenous leukemia
• ABL kinase
• T315I mutant
• Picolinamide
• Benzothiazole
• Antiproliferative

A series of novel picolinamide based benzothiazoles (17 final compounds), targeting both wild-type and the most resistant T315I mutant of Bcr-Abl kinase, has been designed and synthesized. Moreover, a selected array (8 compounds) was evaluated for its antiproliferative activity over a panel of 60 cancer cell lines. Compound 5l was the most potent derivative against both native and T315I mutant ABL with IC50 values of 18.2 and 39.9 nM, respectively, and showed highly selective inhibitory activity (89.8%) towards the Bcr-Abl dependent leukemia cell (K-562) at 10 mu M concentration. Significance of C6-oxypicolinamide moiety and SAR study for the C2 aliphatic side chain of benzothiazole are discussed in detail.

• 出版日期2015-5-15