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Adamantyl thioureas as soluble epoxide hydrolase inhibitors.

ABSTRACT: A series of inhibitors of the soluble epoxide hydrolase (sEH) containing one or two thiourea groups has been developed. Inhibition potency of the described compounds ranges from 50??M to 7.2?nM. 1,7-(Heptamethylene)bis[(adamant-1-yl)thiourea] (6f) was found to be the most potent sEH inhibitor, among the thioureas tested. The inhibitory activity of the thioureas against the human sEH is closer to the value of activity against rat sEH rather than murine sEH. While being less active, thioureas are up to 7-fold more soluble than ureas, which makes them more bioavailable and thus promising as sEH inhibitors.

SUBMITTER: Burmistrov V

PROVIDER: S-EPMC6442743 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Adamantyl thioureas as soluble epoxide hydrolase inhibitors.

Burmistrov Vladimir V Morisseau Christophe C Pitushkin Dmitry D Karlov Dmitry D Fayzullin Robert R RR Butov Gennady M GM Hammock Bruce D BD

Bioorganic & medicinal chemistry letters 20180523 13

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing one or two thiourea groups has been developed. Inhibition potency of the described compounds ranges from 50 μM to 7.2 nM. 1,7-(Heptamethylene)bis[(adamant-1-yl)thiourea] (6f) was found to be the most potent sEH inhibitor, among the thioureas tested. The inhibitory activity of the thioureas against the human sEH is closer to the value of activity against rat sEH rather than murine sEH. While being less active, thioureas are ...[more]

PMID: 29803731

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