Non-imidazole histamine H3 ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H3-antagonists

Eur J Med Chem. 2005 Jan;40(1):15-23. doi: 10.1016/j.ejmech.2004.09.010.

Abstract

In search for a new lead of non-imidazole histamine H3-receptor antagonists, a series of 1[(2-thiazolopyridine)-4-n-propyl]piperazines, the analogous 1-[(2-oxazolopyridine)-4-npropyl]piperazines, 1-[(2-benzothiazole)-4-n-propyl]piperazine and 1-[(2-benzooxazole)4-n-propyl]piperazine were prepared and in vitro tested as H3-receptor antagonists (the electrically evoked contraction of the guinea-pig jejunum). It appeared that by comparison of homologous pairs the thiazolo derivatives have slightly higher activity than their oxazolo analogues. The most potent compound of these series is the 1-(2-thiazolo[4,5-c]pyridine)-4-n-propylpiperazine (3c) with pA2 = 7.25 (its oxazole analogue (4g) showed pA2 = 6.9). The structure-activity relationships for compounds with various positions of the nitrogen in the benzene ring for the thiazoles compared with oxazoles are discussed.

MeSH terms

  • Animals
  • Drug Design
  • Electric Stimulation
  • Guinea Pigs
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / chemistry
  • Histamine Antagonists / pharmacology
  • Humans
  • In Vitro Techniques
  • Intestines
  • Ligands
  • Male
  • Muscle Contraction / drug effects
  • Piperazines / chemical synthesis
  • Piperazines / pharmacology*
  • Receptors, Histamine H3 / chemistry*
  • Structure-Activity Relationship

Substances

  • Histamine Antagonists
  • Ligands
  • Piperazines
  • Receptors, Histamine H3