Synthesis and SAR studies of novel 2-(6-aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3813-7. doi: 10.1016/j.bmcl.2011.04.022. Epub 2011 Apr 13.

Abstract

Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) antagonists are described. 2-(6-Aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and OT. Optimised compound 16 shows a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / chemistry
  • Acetamides / pharmacology
  • Animals
  • Antidiuretic Hormone Receptor Antagonists*
  • Caco-2 Cells
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Inhibitory Concentration 50
  • Male
  • Molecular Structure
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Antidiuretic Hormone Receptor Antagonists
  • Quinazolinones