Synthesis and SAR of N-Chlorophenyl Substituted Piperrazinylethyl-aminomethylpyrazoles as 5-HT3A Inhibitors

Bulletin of the Korean chemical society

In Sung Choi¹  Seung Yeol Nah¹  Hyewhon Rhim¹  Byung Hwan Lee¹  Kyung Il Choi¹  Ghilsoo Nam¹ 

关键词: 5-HT3 receptor;    5-HT3A receptor channel activity;    Novel 5-HT3 receptor channel current blockers;    Chlorophenyl substituted piperazinylethylaminomethylpyrazoles;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

The 5-HT3A receptors are one of ligand-gated ion channels and are known to be involved in visceral pain, anxiety, or anticancer agent-induced nausea and vomiting. In present study, we designed novel skeletons based on the developed 5-HT3 receptor antagonists and evaluated their effects on 5-HT3A receptor channel currents (I5-HT) of a series of pyrazole derivatives having N-chlorophenylpiperazine functionality (6-9). We found that most of N-p-chlorophenyl substituted piperazinyl-pyrazole derivatives (7b, 7c, 7e and 7h) exhibited the high potency for the inhibition of I5-HT, whereas the compound without chloride (6) or with m-chlorophenyl group (a serious of 8 and 9) showed the low potency. These results indicate that p-chlorophenyl group is might play an important role for increasing the inhibitory potency on I5-HT.

【 授权许可】

Unknown