Amfetaminil

Amfetaminil
Clinical data
ATC code
  • none
Legal status
Legal status
Identifiers
  • 2-Phenyl-2-(1-phenylpropan-2-ylamino)acetonitrile
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.037.767 Edit this at Wikidata
Chemical and physical data
FormulaC17H18N2
Molar mass250.345 g·mol−1
3D model (JSmol)
  • N#CC(NC(C)Cc1ccccc1)c2ccccc2
  • InChI=1S/C17H18N2/c1-14(12-15-8-4-2-5-9-15)19-17(13-18)16-10-6-3-7-11-16/h2-11,14,17,19H,12H2,1H3 checkY
  • Key:NFHVTCJKAHYEQN-UHFFFAOYSA-N checkY
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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was developed in the 1970s and used for the treatment of obesity,[2] ADHD,[3][4] and narcolepsy.[5] It has largely been withdrawn from clinical use following problems with abuse.[6] The drug is a prodrug to amphetamine.[7][8]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

Synthesis:[9][10][11][12][13]

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.

References

  1. ^ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 13–. ISBN 978-94-011-4439-1.
  2. ^ 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. PMID 2874966.
  3. ^ 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. PMID 1005547.
  4. ^ 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. PMID 8768943.
  5. ^ Schlesser JL (1991). Drugs Available Abroad - A Guide to Therapeutic Drugs Approved Outside the US. Detroit: MEDEX Books.
  6. ^ 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. PMID 1005549.
  7. ^ Dasgupta A (2 July 2012). Resolving Erroneous Reports in Toxicology and Therapeutic Drug Monitoring: A Comprehensive Guide. John Wiley & Sons. pp. 96–. ISBN 978-1-118-34785-0.
  8. ^ AHC Media, LLC (17 March 2014). Pediatric Trauma Care II: A clinical reference for physicians and nurses caring for the acutely injured child. AHC Media, LLC. pp. 118–. ISBN 978-1-934863-59-6.
  9. ^ 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. PMID 5165569.
  10. ^ Klosa J (August 1975). "[The stability of amphetaminil. Syntheses with amphetaminil (author's transl)]". Arzneimittel-Forschung (in German). 25 (8): 1252–8. PMID 1242355.
  11. ^ Klosa J (1975). "[On the crystallisation of amphetaminil base into its hydrochloride salt (author's transl)]". Arzneimittel-Forschung (in German). 25 (12): 1863–4. PMID 1243655.
  12. ^ Beyer KH, Strassner W, Klinge D. "Amphetaminil [α-(1-benzylethylamino)-α-phenylacetonitrile]". Deutsche Apotheker Zeitung. 111 (19): 677–680.
  13. ^ Kholodov LE (1967). "Sydnones and sydnonimines. XXXV. Salts and exocyclic derivatives of some sydnonimines". Zhurnal Organicheskoi Khimii. 3 (8): 1513–1518.