Indatraline is N-alkylated at the amino group, making it 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 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; it takes a longer time for this chemical to absorb into the body than cocaine.[4]
Synthesisedit
Two main routes have been reported. The first route was reported by Bøgesø and co-workers.[5]
Another method involves the contraction of a dihydronaphthalene (6–6 fused system) to form the 6–5 indane skeleton.[7]
Routes based on 1-indanone-type intermediates are not as simple as a direct reduction of an imine or oxime. The undesirable cis diastereomers are formed instead of the desirable trans isomers. This adds an extra step to the synthetic route. First, the ketones are reduced to mostly cis alcohols. Second, the cis alcohols are converted to the corresponding mesylates, conserving stereochemistry. Third, the mesylates can then be reacted, e.g. with, N-methylbenzylamine, causing a Walden inversion (SN2). Finally, the removal of the benzyl affords the product as a racemic mixture.
^Cho YS, Yen CN, Shim JS, Kang DH, Kang SW, Liu JO, Kwon HJ (October 2016). "Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway". Scientific Reports. 6 (1): 34655. doi:10.1038/srep34655. PMC5046148. PMID 27694974.
^Negus SS, Brandt MR, Mello NK (October 1999). "Effects of the long-acting monoamine reuptake inhibitor indatraline on cocaine self-administration in rhesus monkeys". The Journal of Pharmacology and Experimental Therapeutics. 291 (1): 60–69. PMID 10490887.
^Rothman RB, Partilla JS, Baumann MH, Dersch CM, Carroll FI, Rice KC (March 2000). "Neurochemical neutralization of methamphetamine with high-affinity nonselective inhibitors of biogenic amine transporters: a pharmacological strategy for treating stimulant abuse". Synapse. 35 (3): 222–227. doi:10.1002/(SICI)1098-2396(20000301)35:3<222::AID-SYN7>3.0.CO;2-K. PMID 10657029. S2CID 16190813.
^Gardner EL, Liu X, Paredes W, Giordano A, Spector J, Lepore M, et al. (October 2006). "A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: effects in laboratory rat models relating to addiction". Neuropharmacology. 51 (5): 993–1003. doi:10.1016/j.neuropharm.2006.06.009. PMID 16901516. S2CID 20465584.
^Bøgesø KP, Christensen AV, Hyttel J, Liljefors T (December 1985). "3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake". Journal of Medicinal Chemistry. 28 (12): 1817–28. doi:10.1021/jm00150a012. PMID 2999402.
^Froimowitz M, Wu KM, Moussa A, Haidar RM, Jurayj J, George C, Gardner EL (December 2000). "Slow-onset, long-duration 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake blockers as potential medications to treat cocaine abuse". Journal of Medicinal Chemistry. 43 (26): 4981–92. doi:10.1021/jm000201d. PMID 11150168.
^Silva LF, Siqueira FA, Pedrozo EC, Vieira FY, Doriguetto AC (April 2007). "Iodine(III)-promoted ring contraction of 1,2-dihydronaphthalenes: a diastereoselective total synthesis of (±)-indatraline". Organic Letters. 9 (8): 1433–6. doi:10.1021/ol070027o. PMID 17371034.
December 18, 2023
indatraline, hydrochloride, antidepressive, agent, selective, monoamine, transporter, inhibitor, that, blocks, reuptake, dopamine, norepinephrine, serotonin, with, similar, efficacy, cocaine, this, compound, used, treat, cocaine, addictions, effects, have, slo. Indatraline hydrochloride Lu 19 005 is an antidepressive agent and non selective monoamine transporter inhibitor that blocks the reuptake of dopamine norepinephrine and serotonin with similar efficacy to cocaine 1 This compound may be used to treat cocaine addictions as its effects have a slower onset and a longer duration than those of cocaine 2 Lu 19 005 has been shown to block the action of methamphetamine and MDMA in laboratory experiments 3 IndatralineClinical dataRoutes ofadministrationOralATC codenoneLegal statusLegal statusIn general uncontrolledIdentifiersIUPAC name 1R 3S 3 3 4 dichlorophenyl N methyl 2 3 dihydro 1H inden 1 amineCAS Number86939 10 8 YPubChem CID126280ChemSpider16736639 YUNII4U40Y96J1ZChEMBLChEMBL146332 YCompTox Dashboard EPA DTXSID4043981Chemical and physical dataFormulaC 16H 15Cl 2NMolar mass292 20 g mol 13D model JSmol Interactive imageSMILES Clc1ccc cc1Cl C H 3C C H NC c2ccccc23InChI InChI 1S C16H15Cl2N c1 19 16 9 13 11 4 2 3 5 12 11 16 10 6 7 14 17 15 18 8 10 h2 8 13 16 19H 9H2 1H3 t13 16 m0 s1 YKey SVFXPTLYMIXFRX BBRMVZONSA N Y verify Contents 1 Methylation 2 Synthesis 3 See also 4 ReferencesMethylation editIndatraline is N alkylated at the amino group making it 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 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 it takes a longer time for this chemical to absorb into the body than cocaine 4 Synthesis editTwo main routes have been reported The first route was reported by Bogeso and co workers 5 nbsp The other has been adapted to scale up 6 nbsp Another method involves the contraction of a dihydronaphthalene 6 6 fused system to form the 6 5 indane skeleton 7 Routes based on 1 indanone type intermediates are not as simple as a direct reduction of an imine or oxime The undesirable cis diastereomers are formed instead of the desirable trans isomers This adds an extra step to the synthetic route First the ketones are reduced to mostly cis alcohols Second the cis alcohols are converted to the corresponding mesylates conserving stereochemistry Third the mesylates can then be reacted e g with N methylbenzylamine causing a Walden inversion SN2 Finally the removal of the benzyl affords the product as a racemic mixture See also editSertraline Tametraline IbogamineReferences edit Cho YS Yen CN Shim JS Kang DH Kang SW Liu JO Kwon HJ October 2016 Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR S6 kinase signaling pathway Scientific Reports 6 1 34655 doi 10 1038 srep34655 PMC 5046148 PMID 27694974 Negus SS Brandt MR Mello NK October 1999 Effects of the long acting monoamine reuptake inhibitor indatraline on cocaine self administration in rhesus monkeys The Journal of Pharmacology and Experimental Therapeutics 291 1 60 69 PMID 10490887 Rothman RB Partilla JS Baumann MH Dersch CM Carroll FI Rice KC March 2000 Neurochemical neutralization of methamphetamine with high affinity nonselective inhibitors of biogenic amine transporters a pharmacological strategy for treating stimulant abuse Synapse 35 3 222 227 doi 10 1002 SICI 1098 2396 20000301 35 3 lt 222 AID SYN7 gt 3 0 CO 2 K PMID 10657029 S2CID 16190813 Gardner EL Liu X Paredes W Giordano A Spector J Lepore M et al October 2006 A slow onset long duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse effects in laboratory rat models relating to addiction Neuropharmacology 51 5 993 1003 doi 10 1016 j neuropharm 2006 06 009 PMID 16901516 S2CID 20465584 Bogeso KP Christensen AV Hyttel J Liljefors T December 1985 3 Phenyl 1 indanamines Potential antidepressant activity and potent inhibition of dopamine norepinephrine and serotonin uptake Journal of Medicinal Chemistry 28 12 1817 28 doi 10 1021 jm00150a012 PMID 2999402 Froimowitz M Wu KM Moussa A Haidar RM Jurayj J George C Gardner EL December 2000 Slow onset long duration 3 3 4 dichlorophenyl 1 indanamine monoamine reuptake blockers as potential medications to treat cocaine abuse Journal of Medicinal Chemistry 43 26 4981 92 doi 10 1021 jm000201d PMID 11150168 Silva LF Siqueira FA Pedrozo EC Vieira FY Doriguetto AC April 2007 Iodine III promoted ring contraction of 1 2 dihydronaphthalenes a diastereoselective total synthesis of indatraline Organic Letters 9 8 1433 6 doi 10 1021 ol070027o PMID 17371034 Retrieved from https en wikipedia org w index php title Indatraline amp oldid 1160738047, wikipedia, wiki, book, books, library,
