Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1021/acsmedchemlett.6b00146
Title (Primary) Varying chirality across nicotinic acetylcholine receptor subtypes: selective binding of quinuclidine triazole compounds
Author Sarasamkan, J.; Scheunemann, M.; Apaijai, N.; Palee, S.; Parichatikanond, W.; Arunrungvichian, K.; Fischer, S.; Chattipakorn, S.; Deuther-Conrad, W.; Schüürmann, G.; Brust, P.; Vajragupta, O.
Source Titel ACS Medicinal Chemistry Letters
Year 2016
Department OEC
Volume 7
Issue 10
Page From 890
Page To 895
Language englisch
Keywords click chemistry; Nicotinic acetylcholine receptor; positron emission tomography; quinuclidine anti-1,2,3-triazole
UFZ wide themes RU3;
Abstract The novel quinuclidine anti-1,2,3-triazole derivatives T1T6 were designed based on the structure of QND8. The binding studies revealed that the stereochemistry at the C3 position of the quinuclidine scaffold plays an important role in the nAChR subtype selectivity. Whereas the (R)-enantiomers are selective to α7 over α4β2 (by factors of 44–225) and to a smaller degree over α3β4 (3–33), their (S)-counterparts prefer α3β4 over α4β2 (62–237) as well as over α7 (5–294). The (R)-derivatives were highly selective to α7 over α3β4 subtypes compared to (RS)- and (R)-QND8. The (S)-enantiomers are 5–10 times more selective to α4β2 than their (R) forms. The overall strongest affinity is observed for the (S)-enantiomer binding to α3β4 (Ki, 2.25–19.5 nM) followed by their (R)-counterpart binding to α7 (Ki, 22.5–117 nM), with a significantly weaker (S)-enantiomer binding to α4β2 (Ki, 414–1980 nM) still above the very weak respective (R)-analogue affinity (Ki, 5059–10436 nM).
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=17949
Sarasamkan, J., Scheunemann, M., Apaijai, N., Palee, S., Parichatikanond, W., Arunrungvichian, K., Fischer, S., Chattipakorn, S., Deuther-Conrad, W., Schüürmann, G., Brust, P., Vajragupta, O. (2016):
Varying chirality across nicotinic acetylcholine receptor subtypes: selective binding of quinuclidine triazole compounds
ACS Med. Chem. Lett. 7 (10), 890 - 895 10.1021/acsmedchemlett.6b00146