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ID: ALA3621164

Journal: ACS Med Chem Lett

Title: Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys.

Authors: Hoyt SB, Petrilli W, London C, Liang GB, Tata J, Hu Q, Yin L, van Koppen CJ, Hartmann RW, Struthers M, Wisniewski T, Ren N, Bopp C, Sok A, Cai TQ, Stribling S, Pai LY, Ma X, Metzger J, Verras A, McMasters D, Chen Q, Tung E, Tang W, Salituro G, Buist N, Clemas J, Zhou G, Gibson J, Maxwell CA, Lassman M, McLaughlin T, Castro-Perez J, Szeto D, Forrest G, Hajdu R, Rosenbach M, Xiong Y.

Abstract: Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2 inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like physical properties. In a rhesus pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

CiteXplore: 26288685

DOI: 10.1021/acsmedchemlett.5b00048