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List of aminorex analogues

From Wikipedia, the free encyclopedia

This is a list ofaminorex analogues, also known assubstituted 2-amino-5-aryloxazolines. Aminorex itself is astimulant drug with a 5-phenyl-2-amino-oxazoline structure. It was developed in the 1960s as ananorectic,[1][2][3] but withdrawn from sale after it was discovered that extended use producedpulmonary hypertension, often followed byheart failure, which resulted in a number of deaths.[4] Adesigner drug analogue4-methylaminorex appeared on the illicit market in the late 1980s but did not attract significant popularity due to its steep dose-response curve and tendency to produceseizures.[5][6][7][8]Pemoline, the 4-keto derivative of aminorex, had been discovered several years earlier,[9] and derivatives of this type appeared to be effective stimulants with comparatively low toxicity.[10][11] Pemoline was sold for around 25 years as a therapy forADHD and relief offatigue, before being withdrawn from the market in 2005 because of rare but serious cases ofliver failure.[12][13][14][15] More recently in around 2014 another derivative4,4'-dimethylaminorex started to be sold illicitly, but again swiftly lost popularity due to a spate of fatal overdose cases.[16][17][18] A number of related compounds are known, and new derivatives have continued to appear on the designer drug market.[19][20][21][22][23][24]

List of substituted aminorex derivatives

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StructureCommon nameChemical nameCAS #
Aminorex5-phenyl-4,5-dihydro-1,3-oxazol-2-amine2207-50-3
Rexamino4-phenyl-4,5-dihydro-1,3-oxazol-2-amine52883-35-9
4'-Fluoroaminorex (4'-FAR)5-(4-fluorophenyl)-4,5-dihydro-1,3-oxazol-2-amine2967-77-3
Clominorex5-(4-chlorophenyl)-4,5-dihydro-1,3-oxazol-2-amine3876-10-6
Fluminorex5-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1,3-oxazol-2-amine720-76-3
Methylenedioxyaminorex5-(3,4-methylenedioxyphenyl)-4,5-dihydro-1,3-oxazol-2-amine3865-98-3
2C-B-aminorex (2C-B-AR)5-(2,5-dimethoxy-4-bromophenyl)-4,5-dihydro-1,3-oxazol-2-amine
N,N-Dimethylaminorex (N,N-DMAR)N,N-dimethyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine32968-41-5
Pemoline2-amino-5-phenyl-1,3-oxazol-4(5H)-one2152-34-3
Thozalinone2-(dimethylamino)-5-phenyl-1,3-oxazol-4(5H)-one655-05-0
Fenozolone2-ethylamino-5-phenyl-1,3-oxazol-4-one15302-16-6
Cyclazodone2-(cyclopropylamino)-5-phenyl-1,3-oxazol-4-one14461-91-7
N-Methylcyclazodone2-(cyclopropyl(methyl)amino)-5-phenyl-1,3-oxazol-4-one14461-92-8
Ephedroxane[25](4S,5R)-3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-one16251-46-0
3-Methylaminorex3-methyl-5-phenyl-2-oxazolidinimine75343-73-6
4-Methylaminorex (4-MAR)4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine3568-94-3
4-Ethylaminorex (4-EAR)4-ethyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine1364933-63-0
4-Isopropylaminorex4-isopropyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine
4-Isobutylaminorex4-(2-methylpropyl)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine
4-tert-butylaminorex4-(1,1-dimethylethyl)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine
4,N-Dimethylaminorex (4,N-DMAR)4,5-dihydro-N,4-dimethyl-5-phenyl-2-oxazolamine2207-49-0
3,4-Dimethylaminorex (3,4-DMAR)3,4-dimethyl-5-phenyl-2-oxazolidinimine82485-31-2
4,4'-Dimethylaminorex (4,4'-DMAR)4-methyl-5-(4-methylphenyl)-4,5-dihydro-1,3-oxazol-2-amine1445569-01-6
2'-Fluoro-4-methylaminorex (2F-MAR)4-methyl-5-(2-fluorophenyl)-4,5-dihydro-1,3-oxazol-2-amine
3'-Fluoro-4-methylaminorex (3F-MAR)4-methyl-5-(3-fluorophenyl)-4,5-dihydro-1,3-oxazol-2-amine
4'-Fluoro-4-methylaminorex (4F-MAR)4-methyl-5-(4-fluorophenyl)-4,5-dihydro-1,3-oxazol-2-amine1364933-64-1
4'-Chloro-4-methylaminorex (4C-MAR)4-methyl-5-(4-chlorophenyl)-4,5-dihydro-1,3-oxazol-2-amine
4'-Bromo-4-methylaminorex (4B-MAR)4-methyl-5-(4-bromophenyl)-4,5-dihydro-1,3-oxazol-2-amine
4'-Methoxy-4-methylaminorex (4'-MeO-4-MAR)4-methyl-5-(4-methoxyphenyl)-4,5-dihydro-1,3-oxazol-2-amine1445570-65-9
3',4',5'-Trimethoxy-4-methylaminorex (TM-4-MAR)4-methyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1,3-oxazol-2-amine1445571-92-5
3',4'-Methylenedioxy-4-methylaminorex (MDMAR)4-methyl-5-(3,4-methylenedioyphenyl)-4,5-dihydro-1,3-oxazol-2-amine1445573-16-9

See also

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References

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  1. ^Meschino JA, Poos GI. 2-amino-5,6-dihydro-4H-1,3-oxazines and a process for their preparation. US Patent 3115494, 1961
  2. ^Poos GI. 2-amino-5-aryloxazoline products. US Patent 3161650, 1962
  3. ^Poos GI, Carson JR, Rosenau JD, Roszkowski AP, Kelley NM, Mcgowin J (May 1963). "2-Amino-5-aryl-2-oxazolines. Potent New Anorectic Agents".Journal of Medicinal Chemistry.6 (3):266–272.doi:10.1021/jm00339a011.PMID 14185981.
  4. ^Gurtner HP (1985). "Aminorex and pulmonary hypertension. A review".Cor et Vasa.27 (2–3):160–171.PMID 3928246.
  5. ^Davis FT, Brewster ME (March 1988). "A fatality involving U4Euh, a cyclic derivative of phenylpropanolamine".Journal of Forensic Sciences.33 (2):549–553.doi:10.1520/JFS11971J.PMID 3373171.
  6. ^Bunker CF, Johnson M, Gibb JW, Bush LG, Hanson GR (May 1990). "Neurochemical effects of an acute treatment with 4-methylaminorex: a new stimulant of abuse".European Journal of Pharmacology.180 (1):103–111.doi:10.1016/0014-2999(90)90597-y.PMID 1973111.
  7. ^Gaine SP, Rubin LJ, Kmetzo JJ, Palevsky HI, Traill TA (November 2000). "Recreational use of aminorex and pulmonary hypertension".Chest.118 (5):1496–1497.doi:10.1378/chest.118.5.1496.PMID 11083709.
  8. ^Meririnne E, Kajos M, Kankaanpää A, Koistinen M, Kiianmaa K, Seppälä T (August 2005). "Rewarding properties of the stereoisomers of 4-methylaminorex: involvement of the dopamine system".Pharmacology, Biochemistry, and Behavior.81 (4):715–724.doi:10.1016/j.pbb.2005.04.020.PMID 15982727.S2CID 21142560.
  9. ^Schmidt L, Scheffler H. Central nervous system stimulant. US Patent 2892753, 1957
  10. ^"Hardy RA, Howell CF, Quinones NQ. Method of producing central nervous system stimulation and anorexia. US Patent 3313688, 1964".Archived from the original on 2021-05-31. Retrieved2019-06-14.
  11. ^"Guidicelli DP, Najer H. 5-phenyl-2-cyclopropylamino-4-oxazolinone, and process for making the same. US Patent 3609159, 1967".Archived from the original on 2021-05-31. Retrieved2019-06-14.
  12. ^Marotta PJ, Roberts EA (May 1998). "Pemoline hepatotoxicity in children".The Journal of Pediatrics.132 (5):894–897.doi:10.1016/s0022-3476(98)70329-4.PMID 9602211.
  13. ^Safer DJ, Zito JM, Gardner JE (June 2001). "Pemoline hepatotoxicity and postmarketing surveillance".Journal of the American Academy of Child and Adolescent Psychiatry.40 (6):622–629.doi:10.1097/00004583-200106000-00006.PMID 11392339.
  14. ^Etwel FA, Rieder MJ, Bend JR, Koren G (2008). "A surveillance method for the early identification of idiosyncratic adverse drug reactions".Drug Safety.31 (2):169–180.doi:10.2165/00002018-200831020-00006.PMID 18217792.S2CID 19964105.
  15. ^Shader RI (April 2017)."Risk Evaluation and Mitigation Strategies (REMS), Pemoline, and What Is a Signal?".Clinical Therapeutics.39 (4):665–669.doi:10.1016/j.clinthera.2017.03.008.PMID 28366595.
  16. ^Brandt SD, Baumann MH, Partilla JS, Kavanagh PV, Power JD, Talbot B, et al. (2014)."Characterization of a novel and potentially lethal designer drug (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or 'Serotoni')".Drug Testing and Analysis.6 (7–8):684–695.doi:10.1002/dta.1668.PMC 4128571.PMID 24841869.
  17. ^Coppola M, Mondola R (July 2015)."4,4'-DMAR: chemistry, pharmacology and toxicology of a new synthetic stimulant of abuse".Basic & Clinical Pharmacology & Toxicology.117 (1):26–30.doi:10.1111/bcpt.12399.PMID 25819702.
  18. ^Maier J, Mayer FP, Luethi D, Holy M, Jäntsch K, Reither H, et al. (August 2018)."The psychostimulant (±)-cis-4,4'-dimethylaminorex (4,4'-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters".Neuropharmacology.138:282–291.doi:10.1016/j.neuropharm.2018.06.018.PMID 29908239.S2CID 49274224.
  19. ^Russell BR, Beresford RA, Schmierer DM, McNaughton N, Clark CR (1995). "Stimulus properties of some analogues of 4-methylaminorex".Pharmacology, Biochemistry, and Behavior.51 (2–3):375–378.doi:10.1016/0091-3057(94)00407-a.PMID 7667356.S2CID 28367828.
  20. ^Zheng Y, Russell B, Schmierer D, Laverty R (January 1997)."The effects of aminorex and related compounds on brain monoamines and metabolites in CBA mice".The Journal of Pharmacy and Pharmacology.49 (1):89–96.doi:10.1111/j.2042-7158.1997.tb06758.x.PMID 9120777.S2CID 20224300.
  21. ^McLaughlin G, Morris N, Kavanagh PV, Power JD, Twamley B, O'Brien J, et al. (July 2015)."Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3',4'-methylenedioxy-4-methylaminorex (MDMAR)".Drug Testing and Analysis.7 (7):555–564.doi:10.1002/dta.1732.PMC 5331736.PMID 25331619.
  22. ^Maier J, Mayer FP, Brandt SD, Sitte HH (October 2018)."DARK Classics in Chemical Neuroscience: Aminorex Analogues".ACS Chemical Neuroscience.9 (10):2484–2502.doi:10.1021/acschemneuro.8b00415.PMC 6287711.PMID 30269490.
  23. ^Fabregat-Safont D, Carbón X, Ventura M, Fornís I, Hernández F, Ibáñez M (June 2019)."Characterization of a recently detected halogenated aminorex derivative: para-fluoro-4-methylaminorex (4'F-4-MAR)".Scientific Reports.9 (1): 8314.Bibcode:2019NatSR...9.8314F.doi:10.1038/s41598-019-44830-y.PMC 6549166.PMID 31165778.
  24. ^Rickli A, Kolaczynska K, Hoener MC, Liechti ME (May 2019). "Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 3,4-DMAR".Neurotoxicology.72:95–100.Bibcode:2019NeuTx..72...95R.doi:10.1016/j.neuro.2019.02.011.PMID 30776375.S2CID 73474963.
  25. ^Hikino H, Ogata K, Kasahara Y, Konno C (May 1985). "Pharmacology of ephedroxanes".Journal of Ethnopharmacology.13 (2):175–191.doi:10.1016/0378-8741(85)90005-4.PMID 4021515.
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