Literature

Abstract

To further explore the structure-activity relationships of conformationally constrained tropanes, a number of new biaryl and arylacetylene analogs were designed and synthesized. Some of these compounds such as 3a-b, 3d, 3f-h, 5b, and 7g were found to be highly potent and selective or mixed norepinephrine transporter (NET) inhibitors with Ki values of 0.8-9.4 nM. Moreover, all of these compounds display weak to extremely weak muscarinic receptor binding affinity, indicating that as potential antidepressants, they may overcome certain side effects that are of concern with other antidepressants, which are thought to be mediated by their anticholinergic properties.

DOI： 10.1016/j.bmcl.2005.03.083

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

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

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

Synthesis and Monoamine Transporter Binding Properties of 3α-(Substituted phenyl)nortropane-2β-carboxylic Acid Methyl Esters. Norepinephrine Transporter Selective Compounds

Journal of Medicinal Chemistry 2005.0

3α-(4-Substituted phenyl)nortropane-2β-carboxylic acid methyl esters show selective binding at the norepinephrine transporter