|Systematic (IUPAC) name|
|Molar mass||237.339 g/mol[[Script error: No such module "String".]]|
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Sertraline has been called "3,4-dichloro tametraline". In the case of tametraline the cis diastereomers are totally impotent and are separated from the product because they are an unneeded contaminant (depressing the crystals melting point, etc).
Tametraline is a catecholamine reuptake inhibitor that possesses certain properties that are mandatory for a psychostimulant. The benzhydryl moiety is an eminent feature and will remind viewers of related molecules such as desoxypipradrol. Indatraline is an indanamine analog of tetralin-based tametraline.
"The KMnO4 oxidation 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."
CAN radical induced dimerization of styrene
"A facile one-pot synthesis of 1-amino-4-aryl-tetralin derivatives by the CAN-induced (see also: CAN) cyclodimerization of various styrenes in acetonitrile and acrylonitrile is described."   doi:10.1021/ol0257934
Certain aromatic substitutients have a potentiating effect (e.g. p-Br), whereas others negate the compounds intrinsic activity.
Enantiopurified Trans and Cis Aminotetraline Derivatives
|Enantiopurified 4-aryl-aminotetralins IC50 (μM)|
Interestingly, (±)-sertraline is not entirely SERT selective until it has been resolved into the SS enantiomer.
C.f. "book" values:
In terms of the trans isomers there is relatively marked separation in the activity between the RS and SR 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 MA transporters.
Racemic Cis and Trans Aminotetraline Derivatives
Figures in brackets are for the N-dimethyl congeners. The primary amines are claimed to completely lack any affinity for the transporters.
c.f. "This property can be perceived as a potential advantage in that enhanced synaptosomal DA levels may be equated with undesirable stimulant properties of certain compounds in the trans series."
- EXP-561 (1-amino-4-phenylbicyclo[2.2.2]octane)
- cyproheptadine [4-(5H-dibenz-[a,d]cyclohepten-5-ylidine)-1-methylpiperidine]
- CP-24,441 (1R, 4S-N-methyl- 4-phenyl-1,2,3,4-tetrahydro-1-naphthylamine)
- CP-39,332 (N-methyl-4-phenyl-1,2,3,4-tetrahydro-2- naphthylamine)
Sepracor has tried to patent the trans dichloro analog U.S. Patent 7,105,699
During his 40 years at Pfizer, Koe authored more than 100 articles and papers. ... Koe learned to review previous studies and to build on findings that had failed to lead to successful products. In his early work with serotonin, for example, he studied the chemical tametraline, which proved ineffective as an anti-depressant.
Tests showed the chemical functioned more as a stimulant, a use Pfizer was not interested in pursuing. Although his research had failed to yield the desired result, Koe was convinced that the development of a viable anti-depressant was within reach.
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- Koe, BK; Weissman, A; Welch, WM; Browne, RG (1983). "Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin". The Journal of pharmacology and experimental therapeutics. 226 (3): 686–700. PMID 6310078.
- Koe, BK (1976). "Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain". The Journal of pharmacology and experimental therapeutics. 199 (3): 649–61. PMID 994022.
- Sarges, R; Koe, BK; Weissman, A; Schaefer, JP (1974). "Blockade of heart 3H-norepinephrine up-take by 4-phenyl-1-aminotetralines: implications for the active conformation of imipramine-like drugs". The Journal of pharmacology and experimental therapeutics. 191 (3): 393–402. PMID 4427286.
- Welch, WM; Kraska, AR; Sarges, R; Koe, BK (1984). "Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralins". Journal of medicinal chemistry. 27 (11): 1508–15. doi:10.1021/jm00377a021. PMID 6492080.
- Sarges, R. (1975). "Synthesis of phenyl-substituted 1-aminotetralines". The Journal of Organic Chemistry. 40: 1216–1224. doi:10.1021/jo00897a008.
- Spyraki, C; Fibiger, HC (1981). "Intravenous self-administration of nomifensine in rats: implications for abuse potential in humans". Science (New York, N.Y.). 212 (4499): 1167–8. PMID 7195072.