Pyrazoles as potential histamine H3-receptor antagonists

Article abstract of DOI:10.1002/ardp.19953280513

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 and carbamate moieties as functional groups were synthesized. Reaction of the hydrochloride of 4-(3-hydroxypropyl)pyrazole 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.