Synthesis and structure-activity data of some new epibatidine analogues.
The high-pressure Diels-Alder reaction of N-carbomethyoxypyrroles and phenyl vinyl sulfone affords versatile intermediates for the palladium-catalyzed preparation of new epibatidine analogues. Structure-activity relationships of new epibatidine analogues are presented. High affinities of Ki = 0.81 and 2.6 nM for the [3H]-cytisine rat brain nicotinic acetylcholine binding sites were found for the 5-pyrimidinyl and the 5-(2-amino)-pyrimidinyl epibatidine analogues, respectively.
Seerden
J P
JP
Department of Organic Chemistry, NSR Center for Molecular Structure, Design, and Synthesis, University of Nijmegen, The Netherlands. J.P.G.Seerden@chem.rug.nl
Tulp
M T
MT
Scheeren
H W
HW
Kruse
C G
CG
D000470:Alkaloids / Q000378:metabolism; D000818:Animals; D001392:Azocines; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D015195:Drug Design; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011807:Quinolizines; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007202:Indicators and Reagents; D018722:Nicotinic Agonists; D011725:Pyridines; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C082748:epibatidine