Discovery of benzimidazole oxazolidinediones as novel and selective nonsteroidal mineralocorticoid receptor antagonists.
Basic Information
ID: ALA3576820
Journal: ACS Med Chem Lett
Title: Discovery of benzimidazole oxazolidinediones as novel and selective nonsteroidal mineralocorticoid receptor antagonists.
Authors: Yang C, Balsells J, Chu HD, Cox JM, Crespo A, Ma X, Contino L, Brown P, Gao S, Zamlynny B, Wiltsie J, Clemas J, Lisnock J, Gibson J, Zhou G, Garcia-Calvo M, Bateman TJ, Tong V, Xu L, Crook M, Sinclair P, Shen HC.
Abstract: Elaboration of the oxazolidinedione series led to replacement of the exocyclic amides with substituted benzimidazoles. The structure-activity relationship (SAR) exploration resulted in the discovery of potent and selective nonsteroidal mineralocorticoid receptor (MR) antagonists with significantly improved microsomal stability and pharmacokinetic (PK) profile relative to the HTS hit 1a. One compound 2p possessed comparable efficacy as spironolactone (SPL) at 100 mg/kg (p.o.) in the rat natriuresis model. As such, this series was validated as a lead series for further optimization.
CiteXplore: 25941555
DOI: 10.1021/acsmedchemlett.5b00010
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