Synthesis and biological activity of 4-(diphenylmethyl)-alpha-[(4-quinolinyloxy)methyl]-1-piperazineethanol and related compounds

J Med Chem. 1992 Nov 13;35(23):4442-9. doi: 10.1021/jm00101a022.

Abstract

A series of 4-(diphenylmethyl)-alpha-[(4-quinolinyloxy)methyl]-1-pipe razineethanol and closely related compounds was synthesized and evaluated for cardiac and vascular activity in isolated perfused rat and guinea pig hearts. Compound 1 produced greater inotropic effects in rat hearts than in guinea pig hearts, a phenomenon which was also observed with the prototype agent DPI 201-106. Compound 15 produced an inotropic effect with one-tenth the potency of compound 1. Both compounds 1 and 15 demonstrated direct inotropic and vasodilatory effects when administered iv in anesthetized dogs, although the vasodilatory activity was more pronounced with compound 15 than 1 and DPI compound. Compound 1 lacks the CN moiety which is a key structural requirement in DPI for positive inotropic activity. The synthesis, in vitro, and in vivo evaluations of these agents, and comparative data with DPI-201-106 (compound 17) are reported.

MeSH terms

  • Animals
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / chemistry
  • Cardiotonic Agents / pharmacology
  • Dogs
  • Guinea Pigs
  • Heart / drug effects
  • Hemodynamics / drug effects
  • Myocardial Contraction / drug effects
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Cardiotonic Agents
  • Piperazines
  • Quinolines
  • 4-(diphenylmethyl)-alpha-((quinolinyloxy)methyl)-1-piperazinoethanol
  • DPI 201-106