Aminorex

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Aminorex
Aminorex-2D-skeletal.png
Systematic (IUPAC) name
(RS)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine
Clinical data
Legal status Schedule III (CA) Schedule I (US)
Identifiers
CAS number 2207-50-3 YesY
ATC code None
PubChem CID 16630
DrugBank DB01490
ChemSpider 15767 YesY
UNII 2SH16612I9 YesY
KEGG D02909 YesY
ChEMBL CHEMBL106258 YesY
Chemical data
Formula C9H10N2O 
Mol. mass 162.19
 YesY (what is this?)  (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 It was withdrawn from the market after it was found to cause pulmonary hypertension.[1] In the U.S., it is an illegal Schedule I drug, with no medical use and poor safety profile.

Aminorex, in the 2-amino-5-aryl oxazoline class, was developed by McNeil 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 (U.S. Patent 3,115,494), 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 It was introduced as a prescription appetite suppressant in Germany, Switzerland and Austria in 1965, but was withdrawn in 1972 after it was found to cause pulmonary hypertension in approximately 0.2% of patients, and was linked to a number of deaths.[3]

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.[4] A similar synthesis has been also published.[5]

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. 
  2. ^ US Patent 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. ^ 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. 
  5. ^ 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.