Aminorex

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Aminorex
Skeletal formula
Ball-and-stick model of aminorex
Clinical data
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard100.164.420 Edit this at Wikidata
Chemical and physical data
FormulaC9H10N2O
Molar mass162.192 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  (verify)

Aminorex (Menocil, Apiquel, aminoxaphen, aminoxafen, McN-742) is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension.[1] In the U.S., it is an illegal Schedule I drug, meaning it has high abuse potential, no accepted medical use, and a poor safety profile.

Aminorex, in the 2-amino-5-aryl oxazoline class, was developed by McNeil Laboratories in 1962.[2] It is closely related to 4-methylaminorex. Aminorex has been shown to have locomotor stimulant effects, lying midway between dextroamphetamine and methamphetamine. Aminorex effects have been attributed to the release of catecholamines.[3]

History[edit]

It was discovered in 1962 by Edward John Hurlburt,[4] and was quickly found in 1963 to have an anorectic effect in rats. It was introduced as a prescription appetite suppressant in Germany, Switzerland and Austria in 1965, but was withdrawn in 1972 after it was found to cause pulmonary hypertension in approximately 0.2% of patients, and was linked to a number of deaths.[3][5]

Synthesis[edit]

The synthesis was first reported in a structure-activity relationship study of 2-amino-5-aryl-2-oxazolines, where aminorex was found to be approximately 2.5 times more potent than D-amphetamine sulfate in inducing anorexia in rats, and was also reported to have CNS stimulant effects.

Aminorex rxn mech.png

The racemic synthesis involves addition/cyclization reaction of 2-amino-1-phenylethanol with cyanogen bromide.[6] A similar synthesis has been also published.[7] In a search for a cheaper synthetic route, a German term developed an alternative route[8] which, by using chiral styrene oxide, allows an enantiopure product.

See also[edit]

References[edit]

  1. ^ Gaine SP, Rubin LJ, Kmetzo JJ, Palevsky HI, Traill TA (November 2000). "Recreational use of aminorex and pulmonary hypertension". Chest. 118 (5): 1496–7. doi:10.1378/chest.118.5.1496. PMID 11083709. Archived from the original on 2013-01-12.
  2. ^ ‹See Tfd›US 3161650, "2-Amino-5-Aryloxazoline Products" 
  3. ^ a b Fishman AP. (Jan 1991). "Aminorex to fen/phen - An epidemic foretold". Circulation. 99 (1): 156–161. doi:10.1161/01.CIR.99.1.156. ISSN 0009-7322. PMID 9884392.
  4. ^ ‹See Tfd›US 3115494, "2-amino-5, 6-dihydro-4ii-1, 3-oxazines and a process for their preparation" 
  5. ^ Weigle, DS (June 2003). "Pharmacological therapy of obesity: past, present, and future". The Journal of Clinical Endocrinology and Metabolism. 88 (6): 2462–9. doi:10.1210/jc.2003-030151. PMID 12788841.
  6. ^ Poos GI, Carson JR, Rosenau JD, Roszowski 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.
  7. ^ Ueda S, Terauchi H, Yano A, Ido M, Matsumoto M, Kawasaki M (Jan 2004). "4,5-Disubstituted-1,3-oxazolidin-2-imine derivatives: a new class of orally bioavailable nitric oxide synthase inhibitor". Bioorg. Med. Chem. Lett. 14 (2): 313–316. doi:10.1016/j.bmcl.2003.11.010. PMID 14698148.
  8. ^ DE Patent 2101424 2-amino-5-phenyl-2-oxazoline preparation