| 词条 | Tametraline | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 448234115 | IUPAC_name = (1R,4S)-N-methyl-4-phenyl-1,2,3,4-tetrahydronaphthalen-1-amine | image = Tametraline.svg | width = 175 | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 52760-47-1 | ATC_prefix = none | ATC_suffix = | PubChem = 104180 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 440C8K5Y5K | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 143316 | C=17 | H=19 | N=1 | molecular_weight = 237.339 g/mol | smiles = CN[C@H](CC1)C(C=CC=C2)=C2[C@H]1C3=CC=CC=C3 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C17H19N/c1-18-17-12-11-14(13-7-3-2-4-8-13)15-9-5-6-10-16(15)17/h2-10,14,17-18H,11-12H2,1H3/t14-,17+/m0/s1 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = NVXPZMLRGBVYQV-WMLDXEAASA-N }}Tametraline (CP-24,441) is the parent of a series of chemical compounds investigated at Pfizer that eventually led to the development of sertraline (CP-51,974-1).[1] 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,[2] reverses reserpine induced hypothermia in mice, and blocks uptake of 3H into rat heart.[3] Tametraline is a norepinephrine-dopamine reuptake inhibitor.[4] Indatraline is an indanamine homolog of tetralin-based tametraline, although in the case of indatraline the product is pm-dichlorinated. ChemistryTwo routes have been previously described,[5] one for aryl moieties containing electron withdrawing groups, and one for electron donating groups: {{clear}}{{Cite journal| first1 = R. .| title = Synthesis of phenyl-substituted 1-aminotetralines| journal = The Journal of Organic Chemistry| last1 = Sarges| volume = 40| issue = 9| pages = 1216–1224| year = 1975 | doi = 10.1021/jo00897a008}}"As expected, Friedel-Crafts cyclization of the diarylbutyric acid derivatives # to the most reactive ring was observed with little or none of the alternative isomer being detected." {{clear}}"The KMnO4 oxidation of the 1-aryl-tetralins # was observed to give 4-hydroxy-4-aryltetralones # instead of the expected tetralone # previously reported.[5] As a result of this finding, direct oxidation of Grignard reaction product # was attempted and found to be a more efficient route." See also: {{US Patent|4045488}} (and refs therein: {{DOI|10.1021/ja01193a020}} {{DOI|10.1021/ja01183a058}} {{DOI|10.1021/ja01157a130}} {{DOI|10.1021/ja01635a052}}) cis-/trans-RatioIn the case of 3,4-dichloro product, approximately 50:50 cis-/trans- ratio was achieved, according to the reference.[4] CAN radical induced dimerization of styrene"A facile one-pot synthesis of 1-amino-4-aryl-tetralin derivatives by the CAN-induced (see also: [https://www.organic-chemistry.org/chemicals/oxidations/ceriumammoniumnitrate-can.shtm CAN]) cyclodimerization of various styrenes in acetonitrile and acrylonitrile is described." [https://www.organic-chemistry.org/abstracts/literature/609.shtm] {{DOI|10.1021/ol0257934}} Structure-activity relationshipCertain aromatic substitutients have a potentiating effect (e.g., p-Br), 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 (cf. indatraline, "31,345"), but it is correct that it is a "latentiated" 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{{col-begin|width=auto}}{{col-break}}
The primary amines are claimed to completely lack any affinity for the transporters. See also
References1. ^{{cite journal | last1 = Koe | first1 = BK | last2 = Weissman | first2 = A | last3 = Welch | first3 = WM | last4 = Browne | first4 = RG | title = Sertraline, 1S,4S-N-Methyl-4-(3,4-Dichlorophenyl)-1,2,3,4-Tetrahydro-1-Naphthylamine, a New Uptake Inhibitor with Selectivity for Serotonin | journal = The Journal of Pharmacology and Experimental Therapeutics | date = September 1983 | volume = 226 | issue = 3 | pages = 686–700 | pmid = 6310078 | url = http://biochem.uvm.edu/courses/files/381_fall_2006_sertraline.pdf | accessdate = 10 August 2016}} {{Stimulants}}{{Monoamine reuptake inhibitors}}2. ^{{cite journal | last1 = Koe | first1 = BK | title = Molecular Geometry of Inhibitors of the Uptake of Catecholamines and Serotonin in Synaptosomal Preparations of Rat Brain | journal = The Journal of Pharmacology and Experimental Therapeutics | date = December 1976 | volume = 199 | issue = 3 | pages = 649–61 | pmid = 994022 }} 3. ^{{cite journal | last1 = Sarges | first1 = R | last2 = Koe | first2 = BK | last3 = Weissman | first3 = A | last4 = Schaefer | first4 = JP | title = Blockade of Heart 3H-Norepinephrine Up-take by 4-Phenyl-1-Aminotetralines: Implications for the Active Conformation of Imipramine-Like Drugs | journal = The Journal of Pharmacology and Experimental Therapeutics | date = December 1974 | volume = 191 | issue = 3 | pages = 393–402 | pmid = 4427286 }} 4. ^1 {{cite journal | last1 = Welch | first1 = WM | last2 = Kraska | first2 = AR | last3 = Sarges | first3 = R | last4 = Koe | first4 = BK | title = Nontricyclic Antidepressant Agents Derived from cis- and trans-1-Amino-4-aryltetralins | journal = Journal of Medicinal Chemistry | date = November 1984 | volume = 27 | issue = 11 | pages = 1508–15 | doi = 10.1021/jm00377a021 | pmid = 6492080 }} 5. ^1 {{cite journal | last1 = Sarges | first1 = RA | title = Synthesis of Phenyl-Substituted 1-Aminotetralines | journal = The Journal of Organic Chemistry | date = May 1975 | volume = 40 | issue = 9 | pages = 1216–24 | doi = 10.1021/jo00897a008 }} 6. ^{{cite journal | last1 = Peng | first1 = XQ | last2 = Xi | first2 = ZX | last3 = Li | first3 = X | last4 = Spiller | first4 = K|last5 = Li | first5 = J | last6 = Chun | first6 = L | last7 = Wu | first7 = KM | last8 = Froimowitz | first8 = M | last9 = Gardner | first9 = EL | title = Is Slow-Onset Long-Acting Monoamine Transport Blockade to Cocaine as Methadone is to Heroin? Implication for Anti-Addiction Medications | journal = Neuropsychopharmacology | date = December 2010 | volume = 35 | issue = 13 | pages = 2564–78 | doi = 10.1038/npp.2010.133 | pmid = 20827272 | pmc = 2978747}} 5 : Amines|Norepinephrine-dopamine reuptake inhibitors|Pfizer|Stimulants|Tetralins |
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