2-(4-alkylpiperazin-1-yl)quinolines as a new class of imidazole-free histamine H3 receptor antagonists

J Med Chem. 2005 Jan 13;48(1):306-11. doi: 10.1021/jm040873u.

Abstract

With the aim of identifying structurally novel, centrally acting histamine H(3) antagonists, a series of 2-(4-alkylpiperazin-1-yl)quinolines was prepared. Systematic variation of the substituents led to highly potent histamine H(3) antagonists with low polar surface area and appropriate log P for blood-brain barrier penetration.

MeSH terms

  • Animals
  • Biochemistry / methods
  • Blood-Brain Barrier / drug effects
  • Drug Evaluation, Preclinical / methods
  • Histamine Antagonists / chemistry*
  • Histamine Antagonists / pharmacology*
  • Humans
  • Imidazoles / chemistry
  • Inhibitory Concentration 50
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rats
  • Receptors, Histamine H3 / drug effects*
  • Receptors, Histamine H3 / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Structure-Activity Relationship

Substances

  • Histamine Antagonists
  • Imidazoles
  • Quinolines
  • Receptors, Histamine H3
  • Receptors, Serotonin