Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model.
Bioorg Med Chem Lett
; 29(10): 1168-1172, 2019 05 15.
Article
em En
| MEDLINE
| ID: mdl-30928197
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 Cav3.1 and Cav3.2 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.
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MEDLINE
Assunto principal:
Pirrolidinas
/
Bloqueadores dos Canais de Cálcio
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Canais de Cálcio Tipo T
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Analgésicos
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Neuralgia
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article