Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and SAR of N-Chlorophenyl Substituted Piperrazinylethyl-aminomethylpyrazoles as 5-HT3A Inhibitors

  • Lee, Byung-Hwan (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Choi, In-Sung (Life-Sciences Research Division, Korea Institute of Science and Technology (KIST)) ;
  • Rhim, Hye-Whon (Life-Sciences Research Division, Korea Institute of Science and Technology (KIST)) ;
  • Choi, Kyung-Il (Life-Sciences Research Division, Korea Institute of Science and Technology (KIST)) ;
  • Nah, Seung-Yeol (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Nam, Ghil-Soo (Life-Sciences Research Division, Korea Institute of Science and Technology (KIST))
  • Published : 2009.11.20
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Abstract

5-$HT_{3}$ receptor;5-$HT_{3A}$ receptor channel activity;Novel 5-$HT_{3}$ receptor channel current blockers;Chlorophenyl substituted piperazinylethylaminomethylpyrazoles; The 5-$HT_{3A}$ 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-$HT_{3}$ receptor antagonists and evaluated their effects on 5-$HT_{3A}$ receptor channel currents ($I_{5-HT}$) 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 $I_{5-HT}$, whereas the compound without chloride (6) or with m-chlorophenyl group (a serious of 8 and 9) showed the low potency. These result indicate that p-chlorophenyl group is might play an important role for increasing the inhibitory potency on $I_{5-HT}$.

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References

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