|Chemical and physical data|
|Molar mass||g·mol−1 162.192|
|3D model (JSmol)|
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 It was withdrawn from the market after it was found to cause pulmonary hypertension. 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. 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.
It was discovered in 1962 by Edward John Hurlburt, 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 It was introduced as a prescription appetite suppressant in Germany, Switzerland and Austria in 1965, but was withdrawn in 1972 after it was found to cause pulmonary hypertension in approximately 0.2% of patients, and was linked to a number of deaths.
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.
The racemic synthesis involves addition/cyclization reaction of 2-amino-1-phenylethanol with cyanogen bromide. A similar synthesis has been also published. In a search for a cheaper synthetic route, a German term developed an alternative route which, by using chiral styrene oxide, allows an enantiopure product.
- 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.
- ‹See Tfd›US 3161650, "2-Amino-5-Aryloxazoline Products"
- 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.
- ‹See Tfd›US 3115494, "2-amino-5, 6-dihydro-4ii-1, 3-oxazines and a process for their preparation"
- 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.
- 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.
- 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.
- DE Patent 2101424 2-amino-5-phenyl-2-oxazoline preparation