Literature

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.

DOI： 10.1016/s0960-894x(03)00786-8

Synthesis and pharmacological evaluation of ( Z )-9-(Heteroarylmethylene)-7-azatricyclo[4.3.1.0 3,7 ]decanes: thiophene analogues as potent norepinephrine transporter inhibitors

Bioorganic & Medicinal Chemistry Letters 2003.0

Biaryl Analogues of Conformationally Constrained Tricyclic Tropanes as Potent and Selective Norepinephrine Reuptake Inhibitors: Synthesis and Evaluation of Their Uptake Inhibition at Monoamine Transporter Sites

Journal of Medicinal Chemistry 2003.0

Novel Conformationally Constrained Tropane Analogues by 6-endo-trig Radical Cyclization and Stille Coupling − Switch of Activity toward the Serotonin and/or Norepinephrine Transporter

Journal of Medicinal Chemistry 2000.0

Thiophene derivatives: a new series of potent norepinephrine and serotonin reuptake inhibitors

Bioorganic & Medicinal Chemistry Letters 2002.0

Discovery of novel conformationally constrained tropane-based biaryl and arylacetylene ligands as potent and selective norepinephrine transporter inhibitors and potential antidepressants

Bioorganic & Medicinal Chemistry Letters 2005.0

Further Studies on Conformationally Constrained Tricyclic Tropane Analogues and Their Uptake Inhibition at Monoamine Transporter Sites: Synthesis of (Z)-9-(Substituted arylmethylene)-7-azatricyclo[4.3.1.0<sup>3,7</sup>]decanes as a Novel Class of Serotonin Transporter Inhibitors