| Abstract
| - Methylphenidate analogues, in which the carbomethoxy has been replaced by an alkyl group and with differentphenyl substituents, have been synthesized and tested in monoamine transporter assays. As predicted froma pharmacophore model, most of the RR/SS diastereomers showed high potency as dopamine reuptakeinhibitors. Analogues with a 4-chlorophenyl group and an unbranched initial alkyl atom had consistentlyenhanced selectivity for the dopamine transporter. The most potent compounds were those with a three- orfour-carbon chain. The “inactive” RS/SR diastereomers showed substantial activity when the phenyl substituentwas 3,4-dichloro. On a locomotor assay, one compound was found to have a slow onset and a long durationof action. The activity of these compounds provides additional evidence for a conformational/superpositionmodel of methylphenidate with cocaine-like structures. A ketone analogue, obtained by hydrogenating apreviously described vinylogous amide, had activity similar to that of methylphenidate.
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