- Synthesis and monoamine transporter binding properties of 2,3-cyclo analogues of 3β-(4′-aminophenyl)-2β-tropanemethanol
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A series of cyclo-3β-(4-aminophenyl)-2β-tropanemethanol analogues (5a-m) possessing varying linker groups between the 2- and 3-position on the tropane ring were synthesized and evaluated for their monoamine transporter binding properties. The results show that binding to the dopamine and serotonin transporters (DAT and 5-HTT) is highly dependent on the specific linker used. Cyclo-3β-(4-aminophenyl)-2β-tropanemethanol pimelic acid ester/amide (5b) had an IC50 of 3.8 nM at the DAT. Cyclo-3β-(4-aminophenyl)- 2β-tropanemethanol sebacic acid ester/amide (5e) had a Ki of 1.9 nM at the 5-HTT and was 68- and 737-fold selective for the 5-HTT relative to the DAT and NET. Small changes to the size as well as the electrostatic and hydrophobic properties of the 2,3-linker in 5b or 5e led to much less potent analogues at all three transporters. These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties.
- Carroll, F. Ivy,Blough, Bruce E.,Huang, Xiaodong,Nie, Zhe,Mascarella, S. Wayne,Deschamps, Jeffrey,Navarro, Hernán A.
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p. 4589 - 4594
(2007/10/03)
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- Preparation process of dicarboxylic acid compounds
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Carboxylic acid compounds, each of which has an indene skeleton and represented by the following formula (2) or a fluorene skeleton and represented by the following formula (3), are each prepared by reacting an unsaturated carboxylic acid compound represented by the following formula (1) with indene or fluorene in the presence of a strong base catalyst: wherein R1, R2, R3 and R4 each independently represents an atom or group selected from a hydrogen atom, an alkyl group, an aryl group or a carboxyl group, with the proviso that at least one of R3 and R4 contains a carboxyl group or a salt thereof or a carboxylic ester group.
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