Discovery of novel non-steroidal reverse indole mineralocorticoid receptor antagonists

Bioorg Med Chem Lett. 2016 Jun 15;26(12):2866-2869. doi: 10.1016/j.bmcl.2016.04.052. Epub 2016 Apr 20.

Abstract

Reported herein are a series of reverse indoles that represent novel non-steroidal mineralocorticoid receptor (MR) antagonists. The key structure-activity relationships (SAR) are presented below. This reverse indole series is exemplified by a compound that demonstrated efficacy in an acute natriuresis rodent model comparable to marketed MR antagonists, spironolactone and eplerenone.

Keywords: Eplerenone; Hypertension; Mineralocorticoid receptor antagonist; Spironolactone.

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Mineralocorticoid Receptor Antagonists / chemical synthesis
  • Mineralocorticoid Receptor Antagonists / chemistry
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Molecular Structure
  • Receptors, Mineralocorticoid / metabolism*
  • Structure-Activity Relationship

Substances

  • Indoles
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Mineralocorticoid