Pyrazoles as potential histamine H3-receptor antagonists

Arch Pharm (Weinheim). 1995 May;328(5):469-72. doi: 10.1002/ardp.19953280513.

Abstract

In search of structure-activity relationships among histamine H3-receptor antagonists, the imidazole ring of known H3-receptor antagonists was replaced by different heteroaromatic ring systems. Thus, pyrazoles with ether (4,5) and carbamate (6,7) moieties as functional groups were synthesized. Reaction of the hydrochloride of 4-(3-hydroxypropyl)pyrazole (1) with phenyl or benzyl isocyanates mainly gave the carbamates 6 and 7, whereas a similar reaction with 1 as the free base furnished the N-carbamoylpyrazoles 8 and 9. The bifunctional pyrazoles 10 and 11 were formed as by-products. The compounds obtained did not show significant H3-receptor antagonist activity in vitro (rat brain cortex) or in vivo (mouse brain). These results demonstrate the importance of the imidazole moiety for H3-receptor antagonists. The new compounds were also screened for H1-receptor antagonist activity on the isolated guinea-pig ileum and for H2-receptor antagonist activity on the isolated spontaneously beating guinea-pig right atrium. The substances showed only weak antagonistic activity at both histamine receptors H1 and H2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Guinea Pigs
  • Histamine Antagonists*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Rats

Substances

  • Histamine Antagonists
  • Pyrazoles