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

: Airaksinen AJ, Huotari M, Shvetsov A, Vainiotalo P, Mannisto PT, Tuomisto L, Bergstrom KA, Vepsalainen J

Publisher: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

: 2005

: European Journal of Medicinal Chemistry

: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

: EUR J MED CHEM

: 40

: 3

: 299

: 304

: 6

: 0223-5234

DOI: https://doi.org/10.1016/j.ejmech.2004.11.007

6 beta/7 beta-Methyl-2-methoxycarbonyltropinones (3a, 3b) were synthesized and used as starting materials in the synthesis of 6 beta/7 beta-methyl-2 beta-methoxycarbonyl-3 beta-phenyltropanes (6a, 6b), 6 beta/7 beta-methyl-2 beta-methoxycarbonyl-3 beta-(4-iodo)phenyltropanes (7a, 7b) and 6 beta-methyl-2 beta-methoxycarbonyl-3 beta-(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, 2 beta-carbomethoxy-3 beta-(4-iodo)phenyl-tropane (beta-CIT). (c) 2005 Elsevier SAS. All rights reserved.