NEW RENIN INHIBITORS - STABILITY AND ACTIVITY DETERMINATION. PART IV

Acta Pol Pharm. 2017 Mar;74(2):393-399.

Abstract

A series of new seven potential renin inhibitors containing pseudodipeptides were synthesized. Stability for all compounds (1-7) in homogenates of liver, kidney, lung and in serum, gastric, intestinal juice and in the presence of α-chymotrypsin was determined. Compound 1 was unstable in all determined mediums. Compounds 2, 4, 5 and 7 were unstable, compound 3 was stable, compound 6 was unstable only in α-chy-motrypsin solution. Inhibitory activity of the compounds was measured in vitro by HPLC determination of low-ering concentration of substrate (angiotensinogen) in the presence of renin and the potential renin inhibitor (compounds 1-7). Compounds 1, 2, 4, 5, 6 and 7 showed inhibitory activity (1.12 x 10⁻⁷, 0.96 x 10⁻⁶, 1.58 x10⁻⁷,1.68 x 10⁻⁶, 1.30 x 10⁻⁶, 0.96 x 10⁻⁷M, respectively).

Publication types

  • Comparative Study

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Angiotensinogen / metabolism
  • Antihypertensive Agents / chemistry*
  • Antihypertensive Agents / pharmacology
  • Drug Discovery / methods*
  • Drug Stability
  • Fumarates / chemistry
  • Fumarates / pharmacology
  • Gastric Juice / metabolism
  • Humans
  • Intestinal Secretions / metabolism
  • Kidney / enzymology
  • Liver / enzymology
  • Lung / enzymology
  • Molecular Structure
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Renin / antagonists & inhibitors*
  • Renin / metabolism
  • Structure-Activity Relationship

Substances

  • Amides
  • Antihypertensive Agents
  • Fumarates
  • Protease Inhibitors
  • Angiotensinogen
  • aliskiren
  • Renin