Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands.
A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (K(i) values <2nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).
Gu
Xiaobo
X
Department of Chemistry, University of New Orleans, LA 70148, USA.
Izenwasser
Sari
S
Wade
Dean
D
Housman
Amy
A
Gulasey
Gerard
G
Rhoden
Jill B
JB
Savoie
Christopher D
CD
Mobley
David L
DL
Lomenzo
Stacey A
SA
Trudell
Mark L
ML
D004952:Esters; D008024:Ligands; D008614:Meperidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004952:Esters; D008024:Ligands; D008614:Meperidine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C002752:normeperidine