Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3742-5. doi: 10.1016/j.bmcl.2010.04.068. Epub 2010 Apr 21.

Abstract

A series of biaryl amides containing an azabicyclooctane amine headpiece were synthesized and evaluated as mixed arginine vasopressin (AVP) receptor antagonists. Several analogues, including 8g, 12g, 13d, and 13g, were shown to have excellent V(1a)- and good V(2)-receptor binding affinities. Compound 13d was further profiled for drug-like properties and for an in vitro comparison with conivaptan, the program's mixed V(1a)/V(2)-receptor antagonist standard.

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists*
  • Arginine Vasopressin / antagonists & inhibitors*
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / pharmacology
  • Benzazepines
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Humans
  • Molecular Structure
  • Octanes / chemical synthesis*
  • Octanes / pharmacology
  • Structure-Activity Relationship

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Aza Compounds
  • Benzazepines
  • Bridged Bicyclo Compounds
  • Octanes
  • conivaptan
  • Arginine Vasopressin