The cyano-NNO-azoxy function in the design of an irreversible label for alpha 1 adrenoreceptors

Bioorg Med Chem. 1995 Feb;3(2):173-8. doi: 10.1016/0968-0896(95)00011-5.

Abstract

A potential alpha 1-adrenergic irreversible antagonist 6, containing the cyano-NNO-azoxy function was synthesized and tested. The effects of norepinephrine on rat thoracic aorta were irreversibly blocked by this compound at the concentration of 1 x 10(-5) M after 60 minutes. Binding studies showed that 6, at 1 x 10(-6) M, did not modify the KD of Prazosin and caused a 30% decrease of the Bmax. Substitution in 6 of the bis (2-chloroethyl)amino moiety for the cyano-NNO-azoxy function afforded 7 which behaves as an irreversible antagonist able to change KD of Prazosin without influencing Bmax.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Antagonists / chemical synthesis
  • Adrenergic alpha-Antagonists / chemistry
  • Adrenergic alpha-Antagonists / metabolism
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Drug Design
  • In Vitro Techniques
  • Male
  • Norepinephrine / metabolism
  • Prazosin / analogs & derivatives*
  • Prazosin / antagonists & inhibitors
  • Prazosin / chemical synthesis
  • Prazosin / chemistry
  • Prazosin / metabolism
  • Prazosin / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / metabolism*

Substances

  • 1-(4-amino-6,7--dimethoxy-2-quinazolyl)-4-benzoylpiperazine
  • 1-(4-amino-6,7-dimethoxy-2--quinazolyl)-4-(4-(bis-2-chloroethylamino)benzoyl)piperazine
  • 1-(4-amino-6,7-dimethoxy-2-quinazolyl)-4-(4-(cyano-NNO-azoxy)benzoyl)piperazine
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-1
  • Norepinephrine
  • Prazosin