Synthesis, analgesic activity, and binding properties of some epibatidine analogs with a tropine skeleton.
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-HT1A, 5-HT1B, M1, M2, 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.
Rádl
S
S
Research Institute of Pharmacy and Biochemistry, Prague, Czech Republic.
Hafner
W
W
Budesínsky
M
M
Hejnová
L
L
Krejcí
I
I
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000378:metabolism; D008297:Male; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; C082748:epibatidine