909412-84-6Relevant articles and documents
Synthesis and monoamine transporter binding properties of 2,3-cyclo analogues of 3β-(4′-aminophenyl)-2β-tropanemethanol
Carroll, F. Ivy,Blough, Bruce E.,Huang, Xiaodong,Nie, Zhe,Mascarella, S. Wayne,Deschamps, Jeffrey,Navarro, Hernán A.
, p. 4589 - 4594 (2006)
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.
