Lee, Ju-Hyeon Seo, Seon Hee Lim, Eun Jeong Cho, Nam-Chul Nam, Ghilsoo Kang, Soon Bang Pae, Ae Nim Jeong, Nakcheol Keum, Gyochang 2024-01-20T10:04:21Z 2024-01-20T10:04:21Z 2021-09-05 2014-03-03 0223-5234 https://pubs.kist.re.kr/handle/201004/127010 New tetrahydropyridinyl and piperidinyl ethylamine derivatives were designed with hypothetical mapping on pharmacophore model generated from ligand-based virtual screening. The designed compounds were synthesized, and their inhibitory activities on T-type calcium channel were assayed using FDSS and patch-clamp assay. Among them, compounds 7b and 10b showed potent T-type calcium current blocking activity against Ca(v)3.1 (alpha(1G)) and Ca(v)3.2 (alpha(1H)) channel simultaneously. With hERG and pharmacokinetics studies, compounds 7b and 10b were evaluated for the antinociceptive effect on rat model of neuropathic pain. They were significantly effective in decreasing the pain responses to mechanical and cold allodynia induced by spinal nerve ligation. These results suggest that modulation of alpha(1G) and am subtype T-type calcium channels may provide a promising approach for the treatment of neuropathic pain. (C) 2014 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER CA2+ CHANNELS THERMAL HYPERALGESIA TACTILE ALLODYNIA SENSORY NEURONS CA(V)3.2 INHIBITORS RATS ZONISAMIDE ACTIVATION DISCOVERY Synthesis and biological evaluation of 1-(isoxazol-5-ylmethylaminoethyl)-4-phenyl tetrahydropyridine and piperidine derivatives as potent T-type calcium channel blockers with antinociceptive effect in a neuropathic pain model Article 10.1016/j.ejmech.2013.12.056 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.74, pp.246 - 257 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 74 246 257 scie scopus 000333780800023 2-s2.0-84893194307 Chemistry, Medicinal Pharmacology & Pharmacy Article CA2+ CHANNELS THERMAL HYPERALGESIA TACTILE ALLODYNIA SENSORY NEURONS CA(V)3.2 INHIBITORS RATS ZONISAMIDE ACTIVATION DISCOVERY T-type calcium channel blocker Neuropathic pain Tetrahydropyridine Piperidine Allodynia