Novel adrenoceptor antagonists with a tricyclic pyrrolodipyridazine skeleton

J Med Chem. 1999 Jan 14;42(1):173-7. doi: 10.1021/jm981006q.

Abstract

A still unknown tricyclic heterocyclic system (5) was synthesized from 6-hydroxy-2-methylpyridazin-3-one and its structure identified as 2,8-dichloro-6-methylpyrrolo[1,2-b:3,4-d']dipyridazin-5(6H)- one by spectroscopic investigations. Selective condensation of 5 with 2-[4-(2-substituted-phenyl)piperazin-1-yl]ethylamine gave the 2-arylpiperazinylethylamino-8-chloro derivatives 6a-c, which were investigated in binding studies toward the three alpha1-adrenergic and 5-HT1A-serotonergic receptor subtypes. They displayed high potency on all the assays and some selectivity for alpha1a and alpha1d subtypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / chemical synthesis*
  • Adrenergic Antagonists / chemistry
  • Adrenergic Antagonists / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • CHO Cells
  • Cricetinae
  • Humans
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Pyridazines / pharmacology
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-1 / biosynthesis
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT1
  • Structure-Activity Relationship
  • Vas Deferens / drug effects
  • Vas Deferens / physiology

Substances

  • 8-chloro-2-(2-(4-(2-chlorophenyl)piperazin-1-yl)ethylamino)-6-methylpyrrolo(1,2-b 3,4-d')dipyridazin-5(6H)-one
  • 8-chloro-2-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethylamino)-6-methylpyrrolo(1,2-b 3,4-d')dipyridazin-5(6H)-one
  • 8-chloro-2-(2-(4-phenylpiperazin-1-yl)ethylamino)-6-methylpyrrolo(1,2-b 3,4-d')dipyridazin-5(6H)-one
  • Adrenergic Antagonists
  • Pyridazines
  • Pyrroles
  • Receptors, Adrenergic, alpha-1
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1