Synthesis and monoamine transporter affinity of new 2beta-carbomethoxy-3beta-[aryl or heteroaryl]phenyltropanes.
A series of 16 new 2beta-carbomethoxy-3beta-[aryl or heteroaryl]phenyltropane derivatives was synthesized and evaluated for binding to monoamine transporters. Most of the compounds exhibited nanomolar affinity for the serotonin transporter (SERT). Four compounds presented a particularly attractive pharmacological profile, with very high SERT affinity (K(i) 0.15-0.5 nM) and selectivity versus the dopamine transporter of 25- to 77-fold.
Tamagnan
Gilles
G
Department of Psychiatry, Yale University and VA CT HCS/116A2, 950 Campbell Avenue, West Haven, CT 06516, USA. gtamagnan@indd.org
Alagille
David
D
Fu
Xing
X
Kula
Nora S
NS
Baldessarini
Ross J
RJ
Innis
Robert B
RB
Baldwin
Ronald M
RM
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003042:Cocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D050483:Dopamine Plasma Membrane Transport Proteins / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D016548:Prosencephalon / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry
D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C021278:troparil; D003042:Cocaine