PYRAZOLES AS POTENTIAL HISTAMINE H-3 RECE PTOR ANTAGONISTS

In search of structure-activity relationships among histamine H-3-rece ptor antagonists, the imidazole ring of known H-3-receptor antagonists was replaced by different heteroaromatic ring systems. Thus, pyrazole s with ether (4,5) and carbamate (6,7) moieties as functional groups w ere synthesized. Reaction of the hydrochloride of 4-(3-hydroxypropyl)p yrazole (1) with phenyl or benzyl isocyanates mainly gave the carbamat es 6 and 7, whereas a similar reaction with 1 as the free base furnish ed the N-carbamoylpyrazoles 8 and 9. The bifunctional pyrazoles 10 and 11 were formed as by-products. The compounds obtained did not show si gnificant H-3-receptor antagonist activity in vitro (rat brain cortex) or in vivo (mouse brain). These results demonstrate the importance of the imidazole moiety for H-3-receptor antagonists. The new compounds were also screened for H-1-receptor antagonist activity on the isolate d guinea-pig ileum and for H-2-receptor antagonist activity on the iso lated spontaneously beating guinea-pig right atrium. The substances sh owed only weak antagonistic activity at both histamine receptors H-1 a nd H-2.