Alpha1- and alpha2-adrenoreceptor antagonist profiles of 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles

Chem Biodivers. 2005 Oct;2(10):1290-304. doi: 10.1002/cbdv.200590100.

Abstract

A series of pharmacologically interesting 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles, compounds 1-27, were synthesized (Scheme) and subjected to various biological studies to identify structure-activity relationships (SAR). The new compounds were found to exhibit good non-selective binding affinity towards the alpha1-adrenoreceptor (Table 1). In several cases, high functional antagonism was observed towards the alpha1A-, alpha1B-, and alpha1D-adrenoreceptor subtypes (Table 2). The selectivity for these three subtypes was comparable with or superior to that displayed by the standard drug prazosin. The most-common selectivity rank order was alpha1D > alpha1B > alpha1A, followed by alpha1B > alpha1D > alpha1A. In functional experiments, antagonism towards the alpha2-adrenoreceptor was generally low; however, a few compounds were endowed with significant antagonist properties (pA2 values of up to 7.87).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / chemistry*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / chemistry*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aorta / drug effects
  • Male
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Triazoles / chemistry*
  • Triazoles / pharmacology*
  • Vas Deferens / drug effects

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Triazoles