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ID: ALA4673346

Journal: Bioorg Med Chem Lett

Title: Discovery of a benzimidazole series as the first highly potent and selective ACSL1 inhibitors.

Authors: Hayashi K,Kondo N,Omori N,Yoshimoto R,Hato M,Shigaki S,Nagasawa A,Ito M,Okuno T

Abstract: Long-chain acyl-CoA synthetase-1 (ACSL1), an enzyme that catalyzes the synthesis of long-chain acyl-CoA from the corresponding fatty acids, is believed to play essential roles in lipid metabolism. Structure activity relationship studies based on HTS hit compound 1 delivered the benzimidazole series as the first selective and highly potent ACSL1 inhibitors. Representative compound 13 exhibited not only remarkable inhibitory activity against ACSL1 (IC = 0.042 μM) but also excellent selectivity for the other ACSL isoforms. In addition, compound 13 demonstrated an in vivo suppression effect against the production of long-chain acyl-CoAs in mouse.

CiteXplore: 33285268

DOI: 10.1016/j.bmcl.2020.127722