Remote functionalization of SCH 39166: discovery of potent and selective benzazepine dopamine D1 receptor antagonists

Bioorg Med Chem Lett. 2010 Feb 1;20(3):832-5. doi: 10.1016/j.bmcl.2009.12.094. Epub 2010 Jan 4.

Abstract

A series of novel benzazepine derived dopamine D(1) antagonists have been discovered. These compounds are highly potent at D(1) and showed excellent selectivity over D(2) and D(4) receptors. SAR studies revealed that a variety of functional groups are tolerated on the D-ring of known tetracyclic benzazepine analog 2, SCH 39166, leading to compounds with nanomolar potency at D(1) and good selectivity over D(2)-like receptors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzazepines / chemistry*
  • Benzazepines / pharmacology
  • Dopamine Antagonists / chemistry*
  • Dopamine Antagonists / pharmacology
  • Male
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, Dopamine D1 / physiology

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • ecopipam