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Synthesis, Analgesic Activity, and Binding Properties of Some Epibatidine Analogs with a Tropine Skeleton
Author(s) -
Rádl Stanislav,
Hafner Wieland,
Budeaínsky Milo,
Hejnová Lucie,
Krejcí Ivan
Publication year - 2000
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(20006)333:6<167::aid-ardp167>3.0.co;2-8
Subject(s) - epibatidine , chemistry , moiety , stereochemistry , piperidine , nicotinic acetylcholine receptor , nicotinic agonist , bicyclic molecule , cholinergic , receptor , biochemistry , biology , neuroscience
A series of epibatidine analogs and their positional isomers bearing an 8‐azabicyclo[3.2.1]octane moiety is described. Also some of their simplified analogs bearing a 3‐piperidine moiety are reported. Their receptor binding profiles (5‐HT 1A , 5‐HT 1B , M 1 , M 2 , neuronal nicotinic receptor) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Some of the compounds, especially those containing an 8‐azabicyclo[3.2.1]oct‐2‐ene moiety possess high afinity for the nicotinic cholinergic receptor. The most analgesically active compounds are also highly toxic. Optimized structures (PM3‐MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1—9 were compared with that of epibatidine.