Renin Inhibitory Pentols Showing Improved Enteral Bioavailability

J Med Chem. 1992 Feb 7;35(3):559-67. doi: 10.1021/jm00081a019.

Abstract

Incorporation of a C-terminal pentahydroxy functionality led to potent, low molecular weight hydrophilic renin inhibitors lacking the P1' side chain. As these compounds are easy to synthesize and have sufficient water solubility, they were chosen for further study. Compound 33 was transported across rabbit intestinal brush border membrane vesicles and yielded a hypotensive effect in sodium-depleted rhesus monkeys which lasted for 90 min when dosed at 2 mg/kg id.

MeSH terms

  • Amino Sugars / chemical synthesis*
  • Amino Sugars / pharmacokinetics
  • Amino Sugars / pharmacology
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Biological Availability
  • Blood Pressure / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Intestine, Small / metabolism
  • Lactams
  • Macaca mulatta
  • Male
  • Rabbits
  • Renin / antagonists & inhibitors*
  • Solubility
  • Structure-Activity Relationship
  • Sugar Alcohols / chemical synthesis*
  • Sugar Alcohols / pharmacokinetics
  • Sugar Alcohols / pharmacology

Substances

  • Amino Sugars
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Lactams
  • Sugar Alcohols
  • Renin