Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents.
Variation of the methoxycarbonyl and C-18 substituents of the antiaddictive compound 18-methoxycoronaridine, and contraction of its isoquinuclidine ring segment, provided 15 congeners for SAR evaluation at opioid and alpha3beta4 nicotinic acetylcholine receptors. The opioid activities were relatively low, and the alpha3beta4 nicotinic acetylcholine receptor activities were found to correlate with in vivo antiaddictive activities.
Kuehne
Martin E
ME
Department of Chemistry, University of Vermont, Burlington, Vermont 05405, USA. mkuehne@zoo.uvm.edu
He
Liwen
L
Jokiel
Patrick A
PA
Pace
C J
CJ
Fleck
M W
MW
Maisonneuve
I M
IM
Glick
Stanley D
SD
Bidlack
Jean M
JM
D000818:Animals; D002460:Cell Line; D006801:Humans; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D012646:Self Administration; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D019966:Substance-Related Disorders / Q000188:drug therapy*
C475518:2-methoxyethyl 18-methoxycoronaridinate; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; C403530:nicotinic receptor alpha3beta4; D007050:Ibogaine; C103345:18-methoxycoronaridine