Synthesis and pharmacological evaluation of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes: thiophene analogues as potent norepinephrine transporter inhibitors.
Synthesis and pharmacological evaluation of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes: thiophene analogues as potent norepinephrine transporter inhibitors.
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(Z)-9-(杂芳基亚甲基)-7-氮杂三环[4.3.1.0(3,7)]癸烷的合成和药理学评价：噻吩类似物作为有效的去甲肾上腺素转运蛋白抑制剂。
DOI：
10.1016/s0960-894x(03)00786-8
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发表时间：
2003
影响因子：
2.7
通讯作者：
Kozikowski,AlanP
中科院分区：
文献类型：
--
作者：
Zhou,Jia;Kläss,Thomas;Zhang,Ao;Johnson,KennethM;Wang,ChengZ;Ye,Yanping;Kozikowski,AlanP
To further explore the structure–activity relationships (SARs) of certain tropanes, and to gain insights into the structural features required for high activity and selectivity at norepinephrine transporters (NET), we have introduced both five- and six-membered heteroaromatic moieties such as substituted pyridyl, pyrazinyl, pyrimidyl, thiazolyl, and mono- or disubstituted thienyl groups into conformationally constrained, tricyclic tropane analogues. A number of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.03,7]decanes were synthesized, and their abilities to block dopamine, serotonin, and norepinephrine reuptake by their respective transporters were evaluated. It was found that the five- or six-membered N-containing aromatics are too basic to display high NET activity, while some of the thiophene analogues were identified as potent and selective NET inhibitors.
