Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model

Authors
Son, Woo SeungJeong, Kyu-SungLim, Sang MinPae, Ae Nim
Issue Date
2019-05-15
Publisher
Pergamon Press Ltd.
Citation
Bioorganic & Medicinal Chemistry Letters, v.29, no.10, pp.1168 - 1172
Abstract
Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Ca(v)3.1 and Ca(v)3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain.
Keywords
BIOLOGICAL EVALUATION; MIBEFRADIL BLOCK; SENSORY NEURONS; CLONING; MEMBER; BIOLOGICAL EVALUATION; MIBEFRADIL BLOCK; SENSORY NEURONS; CLONING; MEMBER; Neuropathic pain; T-type calcium channel; Pyrrolidine; Spinal nerve ligation
ISSN
0960-894X
URI
https://pubs.kist.re.kr/handle/201004/119992
DOI
10.1016/j.bmcl.2019.03.026
Appears in Collections:
KIST Article > 2019
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