Optimization of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists and discussion of their binding modes

Bioorg Med Chem. 2009 Dec 15;17(24):8161-7. doi: 10.1016/j.bmc.2009.10.038. Epub 2009 Oct 23.

Abstract

A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V(2) receptor, resulting in the eventual discovery of compound 1g. Molecular modeling of compound 1g with V(2) receptor was also examined to evaluate the binding mode of this series of compounds.

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / pharmacology*
  • Animals
  • Arginine / metabolism
  • Arginine / pharmacology*
  • Arginine Vasopressin / chemistry
  • Arginine Vasopressin / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Receptors, Vasopressin / agonists*
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Receptors, Vasopressin
  • Arginine Vasopressin
  • acetamide
  • Arginine