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A series of 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid esters and amides were prepared and tested for binding to the DAT, SERT, and NET. The achiral compounds were easily attained and found to inhibit DAT binding with K(i)-values ranging from 0.095 to 0.00003 mM. Among the compounds tested 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid 2-methylphenyl ester was found to be highly selective with SERT/DAT>7000; NET/DAT>1700, K(i)=60 nM.

Data from a series of 29 monoamine transport inhibitors were used to generate 2D and 3D QSAR models for their binding affinity to the human dopamine transporter (hDAT). Among the inhibitors were many non-nitrogen containing compounds. The 2D QSAR analysis resulted in the equation −log Ki = 4.00 − 3.93ELUMO − 0.67EHOMO − 3.24σp, which predicted the importance of electron withdrawing groups in the aromatic moiety. However, the model failed to predict the observed poor binding of nitro-substituted compounds. In contrast, a derived 3D QSAR model was capable of predicting these more correctly. Data from a series of 29 monoamine transport inhibitors were used to generate 2D and 3D QSAR models for their binding affinity to the human dopamine transporter (hDAT). Among the inhibitors were many non-nitrogen containing compounds. The 2D QSAR analysis resulted in the equation -log Ki = 4.00 - 3.93ELUMO - 0.67EHOMO - 3.24σp, which predicted the importance of electron withdrawing groups in the aromatic moiety. However, the model failed to predict the observed poor binding of nitro-substituted compounds. In contrast, a derived 3D QSAR model was capable of predicting these more correctly.

A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl carboxylic acid methylesters, were prepared and investigated for their activity towards the dopamine, serotonin and norepinephrine transporters. The compounds were prepared from cyclic ketoesters, which were converted to enolic triflates and reacted with arylboronates using the Suzuki coupling. For comparison the corresponding piperidines were also made and investigated. The new compounds inhibit monoamine-transporters with Ki values ranging from 0.1 to 1000 μM.

A series of 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid esters and amides were prepared and tested for binding to the DAT, SERT, and NET. The achiral compounds were easily attained and found to inhibit DAT binding with K(i)-values ranging from 0.095 to 0.00003 mM. Among the compounds tested 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid 2-methylphenyl ester was found to be highly selective with SERT/DAT>7000; NET/DAT>1700, K(i)=60 nM.