Exploring 1-adamantanamine as an alternative amine moiety for metabolically labile azepane ring in newly synthesized benzo[d]thiazol-2(3H)one σ receptor ligands.
Exploring 1-adamantanamine as an alternative amine moiety for metabolically labile azepane ring in newly synthesized benzo[d]thiazol-2(3H)one σ receptor ligands.
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DOI：
10.1007/s00044-020-02597-2
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
McCurdy CR
中科院分区：
文献类型：
--
作者：
Intagliata S;Agha H;Kopajtic TA;Katz JL;Kamble SH;Sharma A;Avery BA;McCurdy CR
In this work we report the structure-activity relationships, binding properties, and metabolic stability studies of a series of benzo[d]thiazol-2(3H)one as sigma receptors (σRs) ligands. Specifically, to improve the metabolic stability of the cyclic amine fragment of our lead compound (SN56), the metabolically unstable azepane ring was replaced with a 1-adatamantamine moiety. Within the synthesized analogs, compound 12 had low nanomolar affinity for the σ1R (Ki = 7.2 nM) and moderate preference (61-fold) over the σ2R. In vitro metabolic stability studies showed a slight improvement of the metabolic stability for 7-12, even though an extensive metabolism in rat liver microsomes is being observed. Furthermore, metabolic soft spot identification of 12 suggested that the N-methyl group of the adamantyl moiety is a major site of metabolism.
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影响因子：
6.7
作者：
Intagliata, Sebastiano;Alsharif, Walid F.;McCurdy, Christopher R.
通讯作者：
McCurdy, Christopher R.
影响因子：
3.5
作者：
Intagliata, Sebastiano;Modica, Maria N.;Romeo, Giuseppe
通讯作者：
Romeo, Giuseppe
影响因子：
3.3
作者：
Mavlyutov, Timur A.;Duellman, Tyler;Kim, Hung Tae;Epstein, Miles L.;Leese, Charlotte;Davletov, Bazbek A.;Yang, Jay
通讯作者：
Yang, Jay
影响因子：
5.6
作者：
Cirino, Thomas J.;Eans, Shainnel O.;McLaughlin, Jay P.
通讯作者：
McLaughlin, Jay P.
DOI：
10.1124/jpet.118.253484
发表时间：
2019-02-01
影响因子：
3.5
作者：
Nicholson, Hilary E.;Alsharif, Walid F.;Bowen, Wayne D.
通讯作者：
Bowen, Wayne D.