Tametraline is the parent of a series of chemical compounds investigated at Pfizer that eventually led to the development of sertraline. Sertraline has been called "3,4-dichloro-tametraline". This is correct but it is an oversimplification in the sense that sertraline is the S,S-isomer whereas tametraline is the 1R,4S-stereoisomer. 1R-Methylamino-4S-phenyl-tetralin is a potent inhibitor of norepinephrine uptake in rat brain synaptosomes, reverses reserpineinduced hypothermia in mice, and blocks uptake of 3H-Norepinephrine into rat heart. Tametraline is a norepinephrine-dopamine reuptake inhibitor. Indatraline is an indanamine homolog of tetralin-based tametraline, although in the case of indatraline the product is pm-dichlorinated.
Chemistry
Two routes have been previously described, one for aryl moieties containing electron withdrawing groups, and one for electron donating groups: "As expected, Friedel-Craftscyclization of the diarylbutyric acid derivatives # to the most reactive ring was observed with little or none of the alternative isomer being detected." "The KMnO4oxidation of the 1-aryl-tetralins # was observed to give 4-hydroxy-4-aryltetralones # instead of the expected tetralone # previously reported. As a result of this finding, direct oxidation of Grignard reaction product # was attempted and found to be a more efficient route." See also.
''cis''-/''trans''-Ratio
In the case of 3,4-dichloro product, approximately 50:50 cis-/trans- ratio was achieved, according to the reference.
Certain aromatic substitutients have a potentiating effect, whereas others negate the compound's intrinsic activity. It is not right to think of the dimethyl analogs as a "prodrug" to the monomethylated drugs, but it is correct that it is a "" form of the drug. This word is from the salsalate page. This was the reason why sertraline was made only as monomethylated because apparently according to the orders the 1° amine is inactive therefore the drug would have a shorter duration of activity.
Enantiopurified ''trans''- and ''cis''-aminotetraline derivatives
-Sertraline is not entirely SERT selective until it has been resolved into the S,S-enantiomer. In terms of the trans- isomers there is relatively marked separation in the activity between the R,S- and S,R-enantiomers. This stands in contrast to what has been observed in the homologous indamine class where both of the trans- enantiomers possessed significant TRI activity at all three of the monoamine transporters.
Racemic ''cis-'' and ''trans''-aminotetraline derivatives
The primary amines are claimed to completely lack any affinity for the transporters.
