Amfetaminil (also known as amphetaminil, N-cyanobenzylamphetamine,[1] and AN-1; brand name Aponeuron) is a
stimulant drug derived from
amphetamine, which was developed in the 1970s and used for the treatment of
obesity,[2]ADHD,[3][4] and
narcolepsy.[5] It has largely been withdrawn from clinical use following problems with
abuse.[6] The drug is a
prodrug to
amphetamine.[7][8]
Stereochemistry
Amfetaminil is a molecule with two stereogenic centers. Thus, four different stereoisomers exist:
(R)-2-[(R)-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (
CAS number 478392-08-4)
(S)-2-[(S)-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS number 478392-12-0)
(R)-2-[(S)-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS number 478392-10-8)
(S)-2-[(R)-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS number 478392-14-2)
Synthesis
Schiff base formation between amphetamine (1) and benzaldehyde (2) gives benzalamphetamine [2980-02-1] (3). Nucleophilic attack of cyanide anion on the imine (c.f. Strecker reaction) gives amfetaminil (4). Finally, reaction with nitrous acid gives (5). The rearrangement to a
Sydnone then occurs to give
CID:88166659 (6).
Feprosidnine is sans the phenyl group.
^Harris LS (June 1986). "The stimulants and hallucinogens under consideration: a brief overview of their chemistry and pharmacology". Drug and Alcohol Dependence. 17 (2–3): 107–18.
doi:
10.1016/0376-8716(86)90002-5.
PMID2874966.
^Meyer-Probst B, Vehreschild T (August 1976). "[Influencing the lack of concentration in hyperkinetic school children with Aponeuron]". Psychiatrie, Neurologie, und Medizinische Psychologie (in German). 28 (8): 491–9.
PMID1005547.
^Paclt I, Florian J, Brunclíková J, Růzicková I (May 1996). "[Effect of Aponeuron in the treatment of children with hyperkinetic syndrome]". Ceska a Slovenska Psychiatrie (in Czech). 92 (Suppl 1): 41–57.
PMID8768943.
^Schlesser JL (1991). Drugs Available Abroad - A Guide to Therapeutic Drugs Approved Outside the US. Detroit: MEDEX Books.
^Winter E (September 1976). "[Drug abuse and dependence of the amphetamine type with special regard to Amphetaminil (Aponeuron(R))]". Psychiatrie, Neurologie, und Medizinische Psychologie (in German). 28 (9): 513–25.
PMID1005549.
^Yashunskii VG, Gorkin VZ, Mashkovskii MD, Altshuler RA, Veryovkina IV, Kholodov LE (October 1971). "Synthesis and pharmacological effects of some alkyl-, aryl-, and aralkylsydnonimines". Journal of Medicinal Chemistry. 14 (10): 1013–5.
doi:
10.1021/jm00292a042.
PMID5165569.
^Klosa J (August 1975). "[The stability of amphetaminil. Syntheses with amphetaminil (author's transl)]". Arzneimittel-Forschung (in German). 25 (8): 1252–8.
PMID1242355.
^Klosa J (1975). "[On the crystallisation of amphetaminil base into its hydrochloride salt (author's transl)]". Arzneimittel-Forschung (in German). 25 (12): 1863–4.
PMID1243655.
^Beyer KH, Strassner W, Klinge D. "Amphetaminil [α-(1-benzylethylamino)-α-phenylacetonitrile]". Deutsche Apotheker Zeitung. 111 (19): 677–680.
^Kholodov LE (1967). "Sydnones and sydnonimines. XXXV. Salts and exocyclic derivatives of some sydnonimines". Zhurnal Organicheskoi Khimii. 3 (8): 1513–1518.