Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3,4-dihdyro-2(1H)-quinolinone

J Med Chem. 1993 Jul 9;36(14):2011-7. doi: 10.1021/jm00066a010.

Abstract

A series of compounds has been synthesized and demonstrated to be antagonists of V1 receptors both in vitro and in vivo. These compounds are structurally related to the 1-(4-piperidyl)-2(1H)-quinolinones, including OPC-21268, an orally bioavailable AVP V1 antagonist with high V1 specificity. It has been found that the introduction of an acetamide group on the terminal alkoxy chain of 41-44 leads to an increase in oral activity. Certain of these compounds may have efficacy in the study of AVP V1 receptors.

MeSH terms

  • Administration, Oral
  • Animals
  • Antidiuretic Hormone Receptor Antagonists*
  • Binding Sites
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Piperidines / chemical synthesis*
  • Piperidines / metabolism
  • Piperidines / pharmacology
  • Quinolones / chemical synthesis*
  • Quinolones / metabolism
  • Quinolones / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Piperidines
  • Quinolones
  • OPC 21268