Structure activity studies of ring E analogues of methyllycaconitine. Part 2: Synthesis of antagonists to the alpha3beta4* nicotinic acetylcholine receptors through modifications to the ester.
The development of novel agents for the differentiation of neuronal nicotinic acetylcholine receptors (nAChRs) is important for the treatment of a variety of pathological conditions. We have prepared and evaluated a number of simpler analogues of the norditerpeniod alkaloid methyllycaconitine (MLA) in an effort to understand molecular determinants of nAChR*small molecule interactions. We have previously reported the synthesis and evaluation of a series of ring E analogues of MLA. We report here the optimization of the alpha3beta4* functional activity of this series of compounds through modification of the ester.
Bergmeier
Stephen C
SC
Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA. bergmeis@ohio.edu
Ismail
Khadiga A
KA
Arason
Kristjan M
KM
McKay
Susan
S
Bryant
Darrell L
DL
McKay
Dennis B
DB
D000157:Aconitine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000470:Alkaloids / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D002460:Cell Line; D004224:Diterpenes / Q000138:chemical synthesis / Q000494:pharmacology; D004952:Esters / Q000737:chemistry; D018733:Nicotinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002395:Catecholamines; D004224:Diterpenes; D004952:Esters; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C403530:nicotinic receptor alpha3beta4; C054634:methyllycaconitine; D000157:Aconitine