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{{Short description|Amphetamine-derived stimulant drug}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 444359166
| verifiedrevid = 444359166
| IUPAC_name = 2-phenyl-2-(1-phenylpropanyl-2-amino)acetonitrile
| IUPAC_name = 2-Phenyl-2-(1-phenylpropan-2-ylamino)acetonitrile
| image = Amphetaminil Structural Formulae.png
| image = Amphetaminil.svg
| image2 = Amfetaminil.png


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| routes_of_administration =
| routes_of_administration =
| legal_DE = Anlage II
| legal_US = Schedule IV


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 17590-01-1
| CAS_number = 17590-01-1
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0XU0V77JVE
| ATC_prefix = none
| ATC_prefix = none
| PubChem = 28615
| PubChem = 28615
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<!--Chemical data-->
<!--Chemical data-->
| C=17 | H=18 | N=2
| C=17 | H=18 | N=2
| molecular_weight = 250.338
| smiles = N#CC(NC(C)Cc1ccccc1)c2ccccc2
| smiles = N#CC(NC(C)Cc1ccccc1)c2ccccc2
| InChI = 1/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
| InChIKey = NFHVTCJKAHYEQN-UHFFFAOYAR
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChI = 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
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}}
}}


'''Amphetaminil''' ('''Aponeuron, AN-1''') is a [[stimulant]] drug derived from [[amphetamine]], which was developed in the 1970s and used for the treatment of [[obesity]],<ref>Harris LS. The stimulants and hallucinogens under consideration: a brief overview of their chemistry and pharmacology. ''Drug and Alcohol Dependence'' 1986; 17:107.</ref> [[ADHD]],<ref>Meyer-Probst B, Vehreschild T. Influencing the lack of concentration in hyperkinetic schoolchildren with Aponeuron. ''Psychiatrie, Neurologie und Medizinische Psychologie (Leipz)'' 1976; 28:491.</ref><ref>Paclt I, Florian J, Brunclikova J, Ruzickova I. Effect of Aponeuron in the treatment of children with hyperkinetic syndrome. (Czech). ''Ceska a Slovenska Psychiatrie''. 1996 May;92 Suppl 1:41-57.</ref> and [[narcolepsy]].<ref>Schlesser JL. Drugs Available Abroad - A Guide to Therapeutic Drugs Approved Outside the US. MEDEX Books, Detroit, 1991.</ref> It has largely been withdrawn from clinical use following problems with [[drug abuse|abuse]].<ref>Winter E. Drug abuse and dependence of the amphetamine type with special regard to Amphetaminil (Aponeuron(R)). (German). ''Psychiatrie, Neurologie und Medizinische Psychologie (Leipzig)''. 1976 Sep;28(9):513-25.</ref>
'''Amfetaminil''' (also known as '''amphetaminil''', '''''N''-cyanobenzylamphetamine''',<ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA13|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=13–}}</ref> 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]],<ref name="pmid2874966">{{cite journal | vauthors = Harris LS | title = The stimulants and hallucinogens under consideration: a brief overview of their chemistry and pharmacology | journal = Drug and Alcohol Dependence | volume = 17 | issue = 2–3 | pages = 107–18 | date = June 1986 | pmid = 2874966 | doi = 10.1016/0376-8716(86)90002-5 }}</ref> [[ADHD]],<ref name="pmid1005547">{{cite journal | vauthors = Meyer-Probst B, Vehreschild T | title = [Influencing the lack of concentration in hyperkinetic school children with Aponeuron] | language = de | journal = Psychiatrie, Neurologie, und Medizinische Psychologie | volume = 28 | issue = 8 | pages = 491–9 | date = August 1976 | pmid = 1005547 }}</ref><ref name="pmid8768943">{{cite journal | vauthors = Paclt I, Florian J, Brunclíková J, Růzicková I | title = [Effect of Aponeuron in the treatment of children with hyperkinetic syndrome] | language = cs | journal = Ceska a Slovenska Psychiatrie | volume = 92 | pages = 41–57 | date = May 1996 | issue = Suppl 1 | pmid = 8768943 }}</ref> and [[narcolepsy]].<ref>{{cite book | vauthors = Schlesser JL | title = Drugs Available Abroad - A Guide to Therapeutic Drugs Approved Outside the US. | publisher = MEDEX Books | location = Detroit | date = 1991 }}</ref> It has largely been withdrawn from clinical use following problems with [[drug abuse|abuse]].<ref name="pmid1005549">{{cite journal | vauthors = Winter E | title = [Drug abuse and dependence of the amphetamine type with special regard to Amphetaminil (Aponeuron(R))] | language = de | journal = Psychiatrie, Neurologie, und Medizinische Psychologie | volume = 28 | issue = 9 | pages = 513–25 | date = September 1976 | pmid = 1005549 }}</ref> The drug is a [[prodrug]] to [[amphetamine]].<ref name="Dasgupta2012">{{cite book| first = Amitava | last = Dasgupta |title=Resolving Erroneous Reports in Toxicology and Therapeutic Drug Monitoring: A Comprehensive Guide|url=https://books.google.com/books?id=0mD9kKcUU8UC&pg=PT96|date=2 July 2012|publisher=John Wiley & Sons|isbn=978-1-118-34785-0|pages=96–}}</ref><ref name="LLC2014">{{cite book|author=AHC Media, LLC|title=Pediatric Trauma Care II: A clinical reference for physicians and nurses caring for the acutely injured child|url=https://books.google.com/books?id=9fucAwAAQBAJ&pg=PA118|date=17 March 2014|publisher=AHC Media, LLC|isbn=978-1-934863-59-6|pages=118–}}</ref>


== Stereochemistry ==
== Stereochemistry ==
Amphetaminil is a molecule with two stereogenic centers. Thus, four different stereoisomers exist:
Amfetaminil is a molecule with two stereogenic centers. Thus, four different stereoisomers exist:


[[File:Amphetaminil Structural Formulae of four Stereoisomers.png|300px|center]]
[[File:Amphetaminil Structural Formulae of four Stereoisomers.png|420px]]

⚫
* (''R'')-2-[(''R'')-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS-Nr. 478392-08-4)
⚫
* (''S'')-2-[(''S'')-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS-Nr. 478392-12-0)
⚫
* (''R'')-2-[(''S'')-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS-Nr. 478392-10-4)
⚫
* (''S'')-2-[(''R'')-1-Phenylpropan-2-ylamino]-2-phenylacetonitrile (CAS-Nr. 478392-14-2)


⚫
* (''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==
[[File:Amphetaminil synthesis.svg|thumb|center|500px|Synthesis:<ref name="pmid5165569">{{cite journal | vauthors = Yashunskii VG, Gorkin VZ, Mashkovskii MD, Altshuler RA, Veryovkina IV, Kholodov LE | title = Synthesis and pharmacological effects of some alkyl-, aryl-, and aralkylsydnonimines | journal = Journal of Medicinal Chemistry | volume = 14 | issue = 10 | pages = 1013–5 | date = October 1971 | pmid = 5165569 | doi = 10.1021/jm00292a042}}</ref><ref name="pmid1242355">{{cite journal | vauthors = Klosa J | title = [The stability of amphetaminil. Syntheses with amphetaminil (author's transl)] | language = German | journal = Arzneimittel-Forschung | volume = 25 | issue = 8 | pages = 1252–8 | date = August 1975 | pmid = 1242355 | doi = | url = }}</ref><ref name="pmid1243655">{{cite journal | vauthors = Klosa J | title = [On the crystallisation of amphetaminil base into its hydrochloride salt (author's transl)] | language = German | journal = Arzneimittel-Forschung | volume = 25 | issue = 12 | pages = 1863–4 | date = 1975 | pmid = 1243655 | doi = | url = }}</ref><ref>{{cite journal | vauthors = Beyer KH, Strassner W, Klinge D | title = Amphetaminil [α-(1-benzylethylamino)-α-phenylacetonitrile] | journal = Deutsche Apotheker Zeitung | volume = 111 | issue = 19 | pages = 677–680 }}</ref><ref>{{cite journal | vauthors = Kholodov LE | title = Sydnones and sydnonimines. XXXV. Salts and exocyclic derivatives of some sydnonimines. | journal = Zhurnal Organicheskoi Khimii | date = 1967 | volume = 3 | issue = 8 | pages = 1513–1518 }}</ref>]]
[[File:Amphetaminil synthesis.svg|thumb|center|700px|Amphetaminil synthesis:]]
It is synthesized by forming the Schiff's base of amphetamine with benzaldehyde, and then nucleophilic attack on the latter with cyanide anion.<ref>J. Klosa, {{Cite patent|DE|1112987}} (1959); Chem. Abstr., 56: 3409d (1962).</ref>


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 [https://pubchem.ncbi.nlm.nih.gov/compound/88166659 CID:88166659] ('''6'''). [[Feprosidnine]] is sans the phenyl group.
==See also==
*[[Alfetamine]]
*[[Amphecloral]]


== References ==
== References ==
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{{Stimulants}}
{{Stimulants}}
{{Anorectics}}
{{Anorectics}}
{{Monoamine releasing agents}}
{{Catecholaminergics}}
{{Phenethylamines}}
{{Phenethylamines}}


⚫
[[Category:Substituted amphetamines]]
[[Category:Nitriles]]
[[Category:Nitriles]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Prodrugs]]
⚫
[[Category:Substituted amphetamines]]
[[Category:Wakefulness-promoting agents]]
[[Category:World Anti-Doping Agency prohibited substances]]

Latest revision as of 02:40, 22 September 2024

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
 ☒NcheckY (what is this?)  (verify)

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

[edit]

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

[edit]
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

[edit]
  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.
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