Synthesis and biological evaluation of 4-piperidinecarboxylate and 4-piperidinecyanide derivatives for T-type calcium channel blockers |
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Authors: | Woo Hyun Min Lee Yun Suk Roh Eun Joo Seo Seon Hee Song Chi Man Chung Hye Jin Pae Ae Nim Shin Kye Jung |
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Affiliation: | Life/Health Division, Korea Institute of Science and Technology, 5 Wolsong-gil, Seongbuk-gu, Seoul 136-791, Republic of Korea. |
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Abstract: | To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives were prepared and evaluated for in vitro and in vivo activity against α(1G) calcium channel. Among them, several compounds showed good T-type calcium channel inhibitory activity and minimal off-target activity over hERG channel (% inhibition at 10 μM=61.85-71.99, hERG channel IC(50)=1.57 ± 0.14-4.98 ± 0.36 μM). Selected compound 31a was evaluated on SNL model of neuropathic pain and showed inhibitory effect on mechanical allodynia. |
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Keywords: | T-type calcium channel Neuropathic pain |
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