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

Woo Seung Son; Kyu Sung Jeong; Sang Min Lim; Ae Nim Pae

doi:10.1016/j.bmcl.2019.03.026

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

Woo Seung Son, Kyu Sung Jeong, Sang Min Lim, Ae Nim Pae

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1168-1172
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2019.03.026
Publication status	Published - 2019 May 15

Bibliographical note

Funding Information:
This work was supported by the Korea government (MSIP) under the National Research Council of Science & Technology (NST) grant [No. CRC-15-04-KIST ].

Publisher Copyright:
© 2019

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2019.03.026

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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.",

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AU - Pae, Ae Nim

N1 - Funding Information: This work was supported by the Korea government (MSIP) under the National Research Council of Science & Technology (NST) grant [No. CRC-15-04-KIST ]. Publisher Copyright: © 2019

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AB - 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.

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

Abstract

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