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Synthesis and Evaluation of (4‐Chlorobenzhydryl) Piperazine Amides as Sodium Channel Nav1.7 Inhibitors
Author(s) -
Back Seung Keun,
Kam Yoo Lim,
Oh Jung Ae,
Na Heung Sik,
Ih Uhtaek,
Park Choo HeaYoung
Publication year - 2015
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.10446
Subject(s) - neuropathic pain , sodium channel , chemistry , lamotrigine , pharmacology , topical anesthetic , carbamazepine , lidocaine , anticonvulsant , ion channel , sodium , anesthesia , medicine , epilepsy , biochemistry , neuroscience , biology , receptor , organic chemistry
Blockage of voltage‐gated sodium channels is used to treat neuropathic pain which is chronic and can become debilitating. Sodium channels Nav1.7–1.9 are especially attractive targets for drug discovery because of the broad therapeutic potential of their modulation. For a neuropathic pain therapy, anticonvulsant like lamotrigine, carbamazepine and a topical anesthetic such as Lidocaine are used. A growing number of clinical reports suggest that selective inhibitors of Nav1.7 are likely to be the powerful analgesics for treating a broad range of pain conditions. Therefore we evaluated 108 amide derivatives synthesized on human Nav1.7 ( hNav1 .7) by VIPR (voltage/ion probe reader), a fluorescence image plate reader ( FLIPR ) assay that used voltage‐sensor fluorescence dye and stable HEK ‐293 cell lines expressing hNaV1 .7. Ten compounds demonstrated inhibitory activity, and the two most active compounds ( 5 and 6 ) had IC 50 values of 8–10 μM.