Design and pharmacology of quinuclidine derivatives as M2-selective muscarinic receptor ligands.
In our search for M2-selective muscarinic receptor antagonists, we synthesized 1,3-disubstituted indenes. The effects of different basic moieties with regard to binding and selectivity towards the five distinct muscarinic receptor subtypes were investigated. The results show that the quinuclidine series afforded the most promising compounds in terms of both receptor affinity and M2-subtype selectivity.
Böhme
T M
TM
Institute of Pharmacy, University of Mainz, Germany. thomas.boehme@aventis.com
Keim
C
C
Dannhardt
G
G
Mutschler
E
E
Lambrecht
G
G
D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014055:Tomography, Emission-Computed
D008024:Ligands; D011812:Quinuclidines; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic