New V1a receptor antagonist. Part 2. Identification and optimization of triazolobenzazepines

Bioorg Med Chem Lett. 2020 Sep 15;30(18):127417. doi: 10.1016/j.bmcl.2020.127417. Epub 2020 Jul 21.

Abstract

Solid preclinical evidence links vasopressin to social behavior in animals, so, extensive work has been initiated to find new vasopressin V1a receptor antagonists which can improve deteriorated social behavior in humans and can treat the core symptoms of autistic behavior, as well. Our aim was to identify new chemical entities with antagonizing effects on vasopressin V1a receptors. Continuing our previous work, we found an in vitro and in vivo orally active V1a selective antagonist molecule (40) among [1,2,4]triazolo[4,3-a][1]benzazepines.

Keywords: Antagonist; HTS; Synthesis; Triazolobenzazepines; V1a; Vasopressin.

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists / chemical synthesis*
  • Antidiuretic Hormone Receptor Antagonists / pharmacology
  • Benzazepines / chemical synthesis*
  • Benzazepines / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Isomerism
  • Mice
  • Microsomes, Liver / metabolism
  • Protein Binding
  • Quinolones / chemistry
  • Rats
  • Receptors, Vasopressin / metabolism*
  • Social Behavior Disorders / drug therapy*
  • Structure-Activity Relationship

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Quinolones
  • Receptors, Vasopressin