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 It was withdrawn from the market after it was found to cause pulmonary hypertension.[1] In the U.S., it is an illegal Schedule I drug, with no medical use and poor safety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 It was introduced as a prescription appetite suppressant in Germany, Switzerland and Austria in 1965, but was withdrawn in 1972 after it was found to cause pulmonary hypertension in approximately 0.2% of patients, and was linked to a number of deaths.[3]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.
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]
- ^ 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.
- ^ US Patent 3161650 - 2-Amino-5-Aryloxazoline Products
- ^ 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.
- ^ 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.
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