list of aminorex analogues

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This is a list of aminorex analogues, also known as substituted 2-amino-5-aryloxazolines. Aminorex itself is a stimulant drug with a 5-phenyl-2-amino-oxazoline structure. It was developed in the 1960s as an anorectic,[https://patents.google.com/patent/US3115494 Meschino JA, Poos GI. 2-amino-5,6-dihydro-4H-1,3-oxazines and a process for their preparation. US Patent 3115494, 1961][https://patents.google.com/patent/US3161650 Poos GI. 2-amino-5-aryloxazoline products. US Patent 3161650, 1962]{{cite journal | vauthors = Poos GI, Carson JR, Rosenau JD, Roszkowski AP, Kelley NM, Mcgowin J | title = 2-Amino-5-aryl-2-oxazolines. Potent New Anorectic Agents | journal = Journal of Medicinal Chemistry | volume = 6 | issue = 3 | pages = 266–272 | date = May 1963 | pmid = 14185981 | doi = 10.1021/jm00339a011 }} but withdrawn from sale after it was discovered that extended use produced pulmonary hypertension, often followed by heart failure, which resulted in a number of deaths.{{cite journal | vauthors = Gurtner HP | title = Aminorex and pulmonary hypertension. A review | journal = Cor et Vasa | date = 1985 | volume = 27 | issue = 2–3 | pages = 160–171 | pmid = 3928246 }} A designer drug analogue 4-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 produce seizures.{{cite journal | vauthors = Davis FT, Brewster ME | title = A fatality involving U4Euh, a cyclic derivative of phenylpropanolamine | journal = Journal of Forensic Sciences | volume = 33 | issue = 2 | pages = 549–553 | date = March 1988 | doi = 10.1520/JFS11971J | pmid = 3373171 }}{{cite journal | vauthors = Bunker CF, Johnson M, Gibb JW, Bush LG, Hanson GR | title = Neurochemical effects of an acute treatment with 4-methylaminorex: a new stimulant of abuse | journal = European Journal of Pharmacology | volume = 180 | issue = 1 | pages = 103–111 | date = May 1990 | doi = 10.1016/0014-2999(90)90597-y | pmid = 1973111 }}{{cite journal | vauthors = Gaine SP, Rubin LJ, Kmetzo JJ, Palevsky HI, Traill TA | title = Recreational use of aminorex and pulmonary hypertension | journal = Chest | volume = 118 | issue = 5 | pages = 1496–1497 | date = November 2000 | doi = 10.1378/chest.118.5.1496 | pmid = 11083709 }}{{cite journal | vauthors = Meririnne E, Kajos M, Kankaanpää A, Koistinen M, Kiianmaa K, Seppälä T | title = Rewarding properties of the stereoisomers of 4-methylaminorex: involvement of the dopamine system | journal = Pharmacology, Biochemistry, and Behavior | volume = 81 | issue = 4 | pages = 715–724 | date = August 2005 | doi = 10.1016/j.pbb.2005.04.020 | pmid = 15982727 | s2cid = 21142560 }} Pemoline, the 4-keto derivative of aminorex, had been discovered several years earlier,[https://patents.google.com/patent/US2892753 Schmidt L, Scheffler H. Central nervous system stimulant. US Patent 2892753, 1957] and derivatives of this type appeared to be effective stimulants with comparatively low toxicity.{{Cite web |url=https://patents.google.com/patent/US3313688 |title=Hardy RA, Howell CF, Quinones NQ. Method of producing central nervous system stimulation and anorexia. US Patent 3313688, 1964 |access-date=2019-06-14 |archive-date=2021-05-31 |archive-url=https://web.archive.org/web/20210531152352/https://patents.google.com/patent/US3313688 |url-status=live }}{{Cite web |url=https://patents.google.com/patent/US3609159 |title=Guidicelli DP, Najer H. 5-phenyl-2-cyclopropylamino-4-oxazolinone, and process for making the same. US Patent 3609159, 1967 |access-date=2019-06-14 |archive-date=2021-05-31 |archive-url=https://web.archive.org/web/20210531152337/https://patents.google.com/patent/US3609159 |url-status=live }} Pemoline was sold for around 25 years as a therapy for ADHD and relief of fatigue, before being withdrawn from the market in 2005 because of rare but serious cases of liver failure.{{cite journal | vauthors = Marotta PJ, Roberts EA | title = Pemoline hepatotoxicity in children | journal = The Journal of Pediatrics | volume = 132 | issue = 5 | pages = 894–897 | date = May 1998 | doi = 10.1016/s0022-3476(98)70329-4 | pmid = 9602211 }}{{cite journal | vauthors = Safer DJ, Zito JM, Gardner JE | title = Pemoline hepatotoxicity and postmarketing surveillance | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 40 | issue = 6 | pages = 622–629 | date = June 2001 | doi = 10.1097/00004583-200106000-00006 | pmid = 11392339 }}{{cite journal | vauthors = Etwel FA, Rieder MJ, Bend JR, Koren G | title = A surveillance method for the early identification of idiosyncratic adverse drug reactions | journal = Drug Safety | volume = 31 | issue = 2 | pages = 169–180 | year = 2008 | pmid = 18217792 | doi = 10.2165/00002018-200831020-00006 | s2cid = 19964105 }}{{cite journal | vauthors = Shader RI | title = Risk Evaluation and Mitigation Strategies (REMS), Pemoline, and What Is a Signal? | journal = Clinical Therapeutics | volume = 39 | issue = 4 | pages = 665–669 | date = April 2017 | pmid = 28366595 | doi = 10.1016/j.clinthera.2017.03.008 | doi-access = free }} More recently in around 2014 another derivative 4,4'-dimethylaminorex started to be sold illicitly, but again swiftly lost popularity due to a spate of fatal overdose cases.{{cite journal | vauthors = Brandt SD, Baumann MH, Partilla JS, Kavanagh PV, Power JD, Talbot B, Twamley B, Mahony O, O'Brien J, Elliott SP, Archer RP, Patrick J, Singh K, Dempster NM, Cosbey SH | display-authors = 6 | title = Characterization of a novel and potentially lethal designer drug (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or 'Serotoni') | journal = Drug Testing and Analysis | date = 2014 | volume = 6 | issue = 7–8 | pages = 684–695 | doi = 10.1002/dta.1668 | pmid = 24841869 | pmc = 4128571 }}{{cite journal | vauthors = Coppola M, Mondola R | title = 4,4'-DMAR: chemistry, pharmacology and toxicology of a new synthetic stimulant of abuse | journal = Basic & Clinical Pharmacology & Toxicology | volume = 117 | issue = 1 | pages = 26–30 | date = July 2015 | doi = 10.1111/bcpt.12399 | pmid = 25819702 | doi-access = free }}{{cite journal | vauthors = Maier J, Mayer FP, Luethi D, Holy M, Jäntsch K, Reither H, Hirtler L, Hoener MC, Liechti ME, Pifl C, Brandt SD, Sitte HH | display-authors = 6 | title = The psychostimulant (±)-cis-4,4'-dimethylaminorex (4,4'-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters | journal = Neuropharmacology | volume = 138 | pages = 282–291 | date = August 2018 | doi = 10.1016/j.neuropharm.2018.06.018 | pmid = 29908239 | s2cid = 49274224 | doi-access = free }} A number of related compounds are known, and new derivatives have continued to appear on the designer drug market.{{cite journal | vauthors = Russell BR, Beresford RA, Schmierer DM, McNaughton N, Clark CR | title = Stimulus properties of some analogues of 4-methylaminorex | journal = Pharmacology, Biochemistry, and Behavior | date = 1995 | volume = 51 | issue = 2–3 | pages = 375–378 | doi = 10.1016/0091-3057(94)00407-a | pmid = 7667356 | s2cid = 28367828 }}{{cite journal | vauthors = Zheng Y, Russell B, Schmierer D, Laverty R | title = The effects of aminorex and related compounds on brain monoamines and metabolites in CBA mice | journal = The Journal of Pharmacy and Pharmacology | volume = 49 | issue = 1 | pages = 89–96 | date = January 1997 | doi = 10.1111/j.2042-7158.1997.tb06758.x | pmid = 9120777 | s2cid = 20224300 | doi-access = free }}{{cite journal | vauthors = McLaughlin G, Morris N, Kavanagh PV, Power JD, Twamley B, O'Brien J, Talbot B, Dowling G, Mahony O, Brandt SD, Patrick J, Archer RP, Partilla JS, Baumann MH | display-authors = 6 | title = Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3',4'-methylenedioxy-4-methylaminorex (MDMAR) | journal = Drug Testing and Analysis | volume = 7 | issue = 7 | pages = 555–564 | date = July 2015 | doi = 10.1002/dta.1732 | pmid = 25331619 | pmc = 5331736 }}{{cite journal | vauthors = Maier J, Mayer FP, Brandt SD, Sitte HH | title = DARK Classics in Chemical Neuroscience: Aminorex Analogues | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2484–2502 | date = October 2018 | doi = 10.1021/acschemneuro.8b00415 | pmid = 30269490 | pmc = 6287711 }}{{cite journal | vauthors = Fabregat-Safont D, Carbón X, Ventura M, Fornís I, Hernández F, Ibáñez M | title = Characterization of a recently detected halogenated aminorex derivative: para-fluoro-4-methylaminorex (4'F-4-MAR) | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 8314 | date = June 2019 | doi = 10.1038/s41598-019-44830-y | pmid = 31165778 | pmc = 6549166 | bibcode = 2019NatSR...9.8314F }}{{cite journal | vauthors = Rickli A, Kolaczynska K, Hoener MC, Liechti ME | title = Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 3,4-DMAR | journal = Neurotoxicology | volume = 72 | pages = 95–100 | date = May 2019 | doi = 10.1016/j.neuro.2019.02.011 | pmid = 30776375 | bibcode = 2019NeuTx..72...95R | s2cid = 73474963 }}