Synthesis and pharmacological evaluation of (Z)-9-(Heteroarylmethylene)-7-azatricyclo[4.3.1.03,7]decanes: thiophene analogues as potent norepinephrine transporter inhibitors

✍ Scribed by Jia Zhou; Thomas Kläß; Ao Zhang; Kenneth M Johnson; Cheng Z Wang; Yanping Ye; Alan P Kozikowski

• Book ID: 104364088
• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 189 KB
• Volume: 13
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(03)00786-8

✦ Synopsis

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 sixmembered 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[4.3.1.0 3,7 ]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.