alpha(1)-Adrenoceptor antagonists. Rational design, synthesis and biological evaluation of new trazodone-like compounds

Bioorg Med Chem Lett. 2002 Feb 11;12(3):437-40. doi: 10.1016/s0960-894x(01)00772-7.

Abstract

A rational design approach has been applied to synthesize a novel class of compounds with affinity for alpha(1) adrenergic receptors (AR). Molecular structures are characterized by a benzimidazolylpyridazinone or an imidazolylpyridazinone moiety, an original fragment in the field of the arylpiperazine compounds with alpha(1)-AR blocking properties. A 1.1 nM affinity toward alpha(1)-AR was found for compound 3, the most active of this series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists*
  • Alkylation
  • Animals
  • Antidepressive Agents, Second-Generation / chemical synthesis*
  • Antidepressive Agents, Second-Generation / pharmacology
  • Binding, Competitive / drug effects
  • Chemical Phenomena
  • Chemistry, Physical
  • Hydantoins / chemistry
  • Models, Molecular
  • Radioligand Assay
  • Rats
  • Structure-Activity Relationship
  • Trazodone / analogs & derivatives*
  • Trazodone / chemical synthesis*
  • Trazodone / pharmacology

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Antidepressive Agents, Second-Generation
  • Hydantoins
  • Trazodone