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ACS Med Chem Lett. 2015 Mar 6;6(4):461-5. doi: 10.1021/acsmedchemlett.5b00010. eCollection 2015 Apr 9.

Discovery of benzimidazole oxazolidinediones as novel and selective nonsteroidal mineralocorticoid receptor antagonists.

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Merck Research Laboratories, Merck & Co. , Kenilworth, New Jersey 07033, United States.


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.


amide replacement; antagonist; mineralocorticoid receptor; natriuresis effect; oxazolidinedione

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