|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||292.20 g·mol−1|
|3D model (JSmol)|
Indatraline (Lu 19-005) is a non-selective monoamine transporter inhibitor shown to block the reuptake of dopamine, norepinephrine, and serotonin, with effects similar to those of cocaine. The effects have been shown to have a slower onset and longer duration than cocaine, suggesting that the compound may, along with similar compounds, be used for the treatment of cocaine addiction. LU 19-005 has been shown to block the action of methamphetamine and MDMA in laboratory experiments.
Superposition should make it possible to see there is at least a fundamental relationship between the pharmacophore of indatraline and various phenyltropanes.[improper synthesis?]
If indatraline is N-alkylated at the amino group, it is possible to slow the onset of action so that it is not until N-demethylation occurs that the molecules become active. N-methylindatraline has a much longer duration than indatraline because norindatraline is inactive, whereas demethylating N-methylindatraline does not terminate the actions of the parent compound. Effects of N-dimethylindatraline start about 20–30 minutes after administration, making it less likely to be abused than cocaine.
Two main routes have been reported. The first route shown is the original one reported by Bøgesø and co-workers.
the other had been adapted to scale-up:
Another method involves contraction of a dihydronaphthalene (6–6 fused system) to form the 6–5 indane skeleton.
Routes based on 1-indanone types of intermediates are not as simple as a direct reduction of an imine or oxime. It is reported that the undesirable cis diastereomers are formed instead of the desirable trans isomers. This adds an extra step in the synthetic route. First, the ketones are reduced to get mostly cis alcohols. Second, the cis alcohols are converted to the corresponding mesylates conserving stereochemistry. Third, the mesylates can then be reacted with e.g. N-methylbenzylamine, effecting a Walden inversion (SN2). Finally, removal of the benzyl affords the product as a racemic mixture.