Discovery and dimeric approach of novel Natriuretic Peptide Receptor A (NPR-A) agonists

Bioorg Med Chem. 2017 Mar 15;25(6):1762-1769. doi: 10.1016/j.bmc.2017.01.026. Epub 2017 Jan 28.

Abstract

Novel agonists of the Natriuretic Peptide Receptor A (NPR-A) were obtained through random screening and subsequent structural modification of triazine derivatives. The key structural feature to improve in vitro activity was the dimerization of triazine monomer derivatives. The non peptide derivative 7c and 13a showed highly potent NPR-A agonistic activity in vitro and diuretic activity in vivo. These results implied that non-peptidic small molecules open the possibility of new therapy for congestive heart failure.

Keywords: Agonist; Congestive heart failure; Natriuretic Peptide Receptor A; Triazine derivatives.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Cyclic GMP / metabolism
  • Dimerization
  • Diuretics / pharmacology
  • Drug Discovery*
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Mass Spectrometry / methods
  • Molecular Structure
  • Proton Magnetic Resonance Spectroscopy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Atrial Natriuretic Factor / agonists*
  • Structure-Activity Relationship
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Diuretics
  • Triazines
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor A
  • Cyclic GMP