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Synthesis and Pharmacological Evaluation of (Z)-9-(Heteroarylmethylene)-7-azatricyclo[4.3.1.03,7]decanes: Thiophene Analogues as Potent Norepinephrine Transporter Inhibitors.

Texas A&M University - Galveston, Galveston, Texas, United States
Bioorganic & Medicinal Chemistry Letters (Impact Factor: 2.33). 11/2003; 13(20):3565-9. DOI: 10.1016/S0960-894X(03)00786-8
Source: PubMed

ABSTRACT 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[4.3.1.0(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.

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