Synthesis and biological evaluation of 6/7-exo-methyl-3β-(4-iodo)phenyltropane-2β-carboxylic acid methyl esters

6β/7β-Methyl-2-methoxycarbonyltropinones (3a, 3b) were synthesized and used as starting materials in the synthesis of 6β/7β-methyl-2β-methoxycarbonyl-3β-phenyltropanes (6a, 6b), 6β/7β-methyl-2β-methoxycarbonyl-3β-(4-iodo)phenyltropanes (7a, 7b) and 6β-methyl-2β-methoxycarbonyl-3β-(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, 2β-carbomethoxy-3β-(4-iodo)phenyl-tropane (β-CIT).