Benzimidazolone as potent chymase inhibitor: Modulation of reactive metabolite formation in the hydrophobic (P 1) region

…, EM August, L Martin, M Hill-Drzewi…

Index: Lo, Ho Yin; Nemoto, Peter A.; Kim, Jin Mi; Hao, Ming-Hong; Qian, Kevin C.; Farrow, Neil A.; Albaugh, Daniel R.; Fowler, Danielle M.; Schneiderman, Richard D.; Michael August; Martin, Leslie; Hill-Drzewi, Melissa; Pullen, Steven S.; Takahashi, Hidenori; De Lombaert, Stephane Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 15 p. 4533 - 4539

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Citation Number: 6

Abstract

A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P1 hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P1 moiety. Replacement of the benzothiophene with different heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the P1 replacements, benzoisothiazole prevents the ...