- Benzimidazolone as potent chymase inhibitor: modulation of reactive metabolite formation in the hydrophobic (P1) region.
Benzimidazolone as potent chymase inhibitor: modulation of reactive metabolite formation in the hydrophobic (P1) region.
Bioorganic & medicinal chemistry letters (2011-07-08)
Ho Yin Lo, Peter A Nemoto, Jin Mi Kim, Ming-Hong Hao, Kevin C Qian, Neil A Farrow, Daniel R Albaugh, Danielle M Fowler, Richard D Schneiderman, E Michael August, Leslie Martin, Melissa Hill-Drzewi, Steven S Pullen, Hidenori Takahashi, Stéphane De Lombaert
PMID21733690
ABSTRACT
A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P(1) hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P(1) moiety. Replacement of the benzothiophene with different heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the P(1) replacements, benzoisothiazole prevents the formation of GSH conjugate and an in silico analysis of oxidative potentials agreed with the experimental outcome.
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