Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/j.ejmech.2015.05.033
Title (Primary) New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure
Author Barthel, C.; Sorger, D.; Deuther-Conrad, W.; Scheunemann, M.; Schweiger, S.; Jäckel, P.; Roghani, A.; Steinbach, J.; Schüürmann, G.; Sabri, O.; Brust, P.; Wenzel, B.
Source Titel European Journal of Medicinal Chemistry
Year 2015
Department OEC
Volume 100
Page From 50
Page To 67
Language englisch
UFZ wide themes RU3;
Abstract To verify vesamicol as lead structure in the development of radioligands for imaging of VAChT in the brain by PET, we systematically modified this molecule and investigated four different groups of derivatives. Structural changes were conducted in all three ring systems A, B, and C resulting in a library of different vesamicol analogs. Based on their in vitro binding affinity toward VAChT as well as sigma(1) and sigma(2) receptors, we performed a structure-affinity relationship (SAR) study regarding both affinity and selectivity. The compounds possessed VAChT affinities in the range of 132 nM (benzovesamicol) to >10 mu M and selectivity factors from 0.1 to 73 regarding sigma(1) and sigma(2) receptors, respectively. We could confirm the exceptional position of benzovesamicols as most affine VAChT ligands. However, we also observed that most of the compounds with high VAChT affinity demonstrated considerable affinity in particular to the sigma(1) receptor. Finally, none of the various vesamicol analogs in all four groups showed an in vitro binding profile suitable for specific VAChT imaging in the brain.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=16412
Barthel, C., Sorger, D., Deuther-Conrad, W., Scheunemann, M., Schweiger, S., Jäckel, P., Roghani, A., Steinbach, J., Schüürmann, G., Sabri, O., Brust, P., Wenzel, B. (2015):
New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure
Eur. J. Med. Chem. 100 , 50 - 67