Novel design of nonpeptide AVP V(2) receptor agonists: structural requirements for an agonist having 1-(4-aminobenzoyl)-2,3,4, 5-tetrahydro-1H-1-benzazepine as a template

J Med Chem. 2000 Nov 16;43(23):4388-97. doi: 10.1021/jm000108p.

Abstract

The discovery of a series of nonpeptide arginine vasopressin V(2) receptor agonists is described. After identifying the aniline derivative 8 as our lead compound from the metabolites of compound 7 that showed antidiuretic activity by po administration to Brattleboro rats, improvements in the in vitro potency involving evaluations of the structural requirements for agonist action and optimizing the structure of the benzoyl moiety have been intensively undertaken. These studies led to compounds 16g, 19a, and 23b,h,i that show potent agonist activity for the V(2) receptor.

MeSH terms

  • Administration, Oral
  • Animals
  • Arginine Vasopressin / metabolism*
  • Benzazepines / chemical synthesis*
  • Benzazepines / chemistry
  • Benzazepines / pharmacology
  • Cyclic AMP / biosynthesis
  • Diuresis / drug effects
  • Drug Design
  • Female
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Radioligand Assay
  • Rats
  • Receptors, Vasopressin / agonists*
  • Receptors, Vasopressin / metabolism
  • Structure-Activity Relationship

Substances

  • Benzazepines
  • Receptors, Vasopressin
  • Arginine Vasopressin
  • Cyclic AMP