Synthesis and biological evaluation of 6/7-exo-methyl-3beta-(4-iodo)phenyltropane-2beta-carboxylic acid methyl esters.
6beta/7beta-Methyl-2-methoxycarbonyltropinones (3a, 3b) were synthesized and used as starting materials in the synthesis of 6beta/7beta-methyl-2beta-methoxycarbonyl-3beta-phenyltropanes (6a, 6b), 6beta/7beta-methyl-2beta-methoxycarbonyl-3beta-(4-iodo)phenyltropanes (7a, 7b) and 6beta-methyl-2beta-methoxycarbonyl-3beta-(4-iodo)phenylnortropane (8). The effect of 6/7-groups was evaluated by in vitro receptor binding to dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters. Introduction of a methyl group at the 6- or 7-position diminished the overall affinity for the transporters, though mostly to NET. In vivo locomotor tests were performed in mice for compounds 7a and 8. Compound 8 had no apparent effect on locomotor activity. Compound 7a increased locomotion in a wide dose range, but was much less potent than a reference compound, 2beta-carbomethoxy-3beta-(4-iodo)phenyl-tropane (beta-CIT).
Airaksinen
Anu J
AJ
Department of Chemistry, University of Kuopio, P.O.B. 1627, 70211 Kuopio, Finland. anu.airaksinen@uku.fi
Huotari
Marko
M
Shvetsov
Alexander
A
Vainiotalo
Pirjo
P
Männisto
Pekka T
PT
Tuomisto
Leena
L
Bergström
Kim A
KA
Vepsäläinen
Jouko
J
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000378:metabolism
C503167:6-methyl-3-(4-iodo)phenyltropane-2-carboxylic acid methyl ester; C503168:7-methyl-3-(4-iodo)phenyltropane-2-carboxylic acid methyl ester; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493228:Slc6a2 protein, mouse; C493226:Slc6a2 protein, rat; C493215:Slc6a3 protein, mouse; C493216:Slc6a3 protein, rat; C493231:Slc6a4 protein, mouse; C493232:Slc6a4 protein, rat; D027981:Symporters; D003042:Cocaine