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{{Short description|Antipsychotic medication}}
{{Short description|Antipsychotic medication}}
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| legal_status = Withdrawn<ref name="Dixit">{{Cite journal | vauthors = Dixit N, Patel C, Bhavsar M, Patel S, Rawal R, Solanki H |date=2022-05-02 |title=Quantitative Structure-activity Relationship (QSAR) study of Liver Toxic Drugs |journal=International Association of Biologicals and Computational Digest |volume=1 |pages=63–71 |doi=10.56588/iabcd.v1i1.17 |eissn=2583-3995 |doi-access=free}}</ref>
| legal_UK= Withdrawn<ref name="Dixit">{{Cite journal | vauthors = Dixit N, Patel C, Bhavsar M, Patel S, Rawal R, Solanki H |date=2022-05-02 |title=Quantitative Structure-activity Relationship (QSAR) study of Liver Toxic Drugs |journal=International Association of Biologicals and Computational Digest |volume=1 |pages=63–71 |doi=10.56588/iabcd.v1i1.17 |eissn=2583-3995 |doi-access=free}}</ref>


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'''Clomacran''' is an [[antipsychotic drug]] of the [[acridine]]s class, developed in the 1970s<ref name="Elks"/> by the pharmaceutical company [[Smith, Kline & French]] under the brand names Devryl and Olaxin.<ref name="chemicalbook"/>
'''Clomacran''' is an [[antipsychotic drug]] of the dihydro[[acridine]] class, developed in the 1970s<ref name="Elks"/> by the pharmaceutical company [[Smith, Kline & French]] (now [[GlaxoSmithKline]]) under the brand names Devryl and Olaxin.<ref name="chemicalbook"/>

⚫
It was used to treat schizophrenia in the 70s.<ref>{{cite journal | vauthors = Pecknold JC, Ban TA, Lehmann HE, Climan M | title = Clomacran in the treatment of schizophrenic patients: a comparison of two assessment methods | journal = International Journal of Clinical Pharmacology and Biopharmacy | volume = 11 | issue = 4 | pages = 299–303 | date = June 1975 | pmid = 1099021 }}</ref> It was withdrawn from the market in the UK, due to liver toxicity, in 1982.<ref name="Dixit" /><ref name="PubChem">{{Cite web |title=Clomacran |url= https://pubchem.ncbi.nlm.nih.gov/compound/21382 |access-date=2023-08-25 | work = PubChem |language=en | publisher = U.S. National Library of Medicine }}</ref><ref>{{Cite book |title=Mann's Pharmacovigilance |date=2014 |publisher=Wiley |isbn=978-0-470-67104-7 | veditors = Andrews EB, Moore N |edition=1st |language=en |doi=10.1002/9781118820186 }}</ref>


⚫
It was been used to treat schizophrenia in the 70s.<ref>{{Cite journal |last=Pecknold |first=J. C. |last2=Ban |first2=T. A. |last3=Lehmann |first3=H. E. |last4=Climan |first4=M. |date=1975 |title=Clomacran in the treatment of schizophrenic patients: a comparison of two assessment methods |url=https://pubmed.ncbi.nlm.nih.gov/1099021/ |journal=International Journal of Clinical Pharmacology and Biopharmacy |volume=11 |issue=4 |pages=299–303 |issn=0340-0026 |pmid=1099021}}</ref> It was withdrawn from the market in the UK, due to liver toxicity, in 1982.<ref name="Dixit" /><ref name="PubChem">{{Cite web |title=Clomacran |url= https://pubchem.ncbi.nlm.nih.gov/compound/21382 |access-date=2023-08-25 | work = PubChem |language=en | publisher = U.S. National Library of Medicine }}</ref><ref>{{Cite book |title=Mann's Pharmacovigilance |date=2014 |publisher=Wiley |isbn=978-0-470-67104-7 | veditors = Andrews EB, Moore N |edition=1st |language=en |doi=10.1002/9781118820186 }}</ref>
==Synthesis==
==Synthesis==
[[File:Clomacran synthesis.svg|thumb|center|500px|Patents:<ref>Zirkle Charles L, {{US patent|3131190}} (1964 to Smith Kline French Lab).</ref><ref>E Anderson & H Graboyes, {{US patent|3781358}} (1973 to SmithKline Beecham Corp).</ref><ref>Elvin L Anderson & Harold Graboyes, {{US patent|3692834}} (1972 to Smith Kline and French Laboratories Ltd, GlaxoSmithKline LLC SmithKline Beecham Corp).</ref><ref>Elvin L Anderson & Harold Graboyes, {{US patent|3919312}} (1975 to SmithKline Beecham Corp).</ref>]]
[[File:Clomacran synthesis.svg|thumb|center|500px|Patents:<ref>Zirkle Charles L, {{US patent|3131190}} (1964 to Smith Kline French Lab).</ref><ref>E Anderson & H Graboyes, {{US patent|3781358}} (1973 to SmithKline Beecham Corp).</ref><ref>Elvin L Anderson & Harold Graboyes, {{US patent|3692834}} (1972 to Smith Kline and French Laboratories Ltd, GlaxoSmithKline LLC SmithKline Beecham Corp).</ref><ref>Elvin L Anderson & Harold Graboyes, {{US patent|3919312}} (1975 to SmithKline Beecham Corp).</ref>]]


The first step involves FGI of 3-chloro-N,N-dimethylpropylamine Fb: [109-54-6] ('''2''') into the Grignard reagent, i.e. (3-(Dimethylamino)propyl)magnesium chloride [19070-16-7] ([154034-91-0]). The Grignard reaction with 2-chloroacridone [7497-52-1] ('''1''') affords the tertiary carbinol ('''3'''). Dehydration by means of acid or simply heat gives the corresponding olefin ('''4'''). Catalytic reduction completes the synthesis of the tranquilizer, clomacran ('''5''').
The first step involves FGI of 3-chloro-N,N-dimethylpropylamine Fb: [109-54-6] ('''2''') into the Grignard reagent, i.e. (3-(Dimethylamino)propyl)magnesium chloride [19070-16-7] ([154034-91-0]). The Grignard reaction with 2-chloroacridone [7497-52-1] ('''1''') affords the tertiary carbinol ('''3'''). Dehydration by means of acid or simply heat gives the corresponding olefin ('''4'''). Catalytic reduction completes the synthesis of ('''5''').


== References ==
== References ==

Latest revision as of 17:42, 25 June 2024

Clomacran
Clinical data
Trade namesDevryl, Olaxin,[1] Develar[2][3]
ATC code
Legal status
Legal status
Identifiers
  • 3-(2-chloro-9,10-dihydroacridin-9-yl)-N,N-dimethylpropan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H21ClN2
Molar mass300.83 g·mol−1
3D model (JSmol)
Density1.120 g/cm3 [1]
  • CN(C)CCCC1C2=CC=CC=C2NC3=C1C=C(C=C3)Cl
  • InChI=1S/C18H21ClN2/c1-21(2)11-5-7-14-15-6-3-4-8-17(15)20-18-10-9-13(19)12-16(14)18/h3-4,6,8-10,12,14,20H,5,7,11H2,1-2H3 checkY
  • Key:JFRLWWDJCFYFSU-UHFFFAOYSA-N checkY

Clomacran is an antipsychotic drug of the dihydroacridine class, developed in the 1970s[2] by the pharmaceutical company Smith, Kline & French (now GlaxoSmithKline) under the brand names Devryl and Olaxin.[1]

It was used to treat schizophrenia in the 70s.[6] It was withdrawn from the market in the UK, due to liver toxicity, in 1982.[4][7][8]

Synthesis[edit]

Patents:[9][10][11][12]

The first step involves FGI of 3-chloro-N,N-dimethylpropylamine Fb: [109-54-6] (2) into the Grignard reagent, i.e. (3-(Dimethylamino)propyl)magnesium chloride [19070-16-7] ([154034-91-0]). The Grignard reaction with 2-chloroacridone [7497-52-1] (1) affords the tertiary carbinol (3). Dehydration by means of acid or simply heat gives the corresponding olefin (4). Catalytic reduction completes the synthesis of (5).

References[edit]

  1. ^ a b c "Clomacran | 5310-55-4". ChemicalBook. Retrieved 2023-08-25.
  2. ^ a b Elks J, Ganellin CR, eds. (1990). Dictionary of Drugs. Boston, MA: Springer US. p. 297. doi:10.1007/978-1-4757-2085-3. ISBN 978-1-4757-2087-7.
  3. ^ "Substâncias e remédios sob controle" [Substances and drugs under control] (PDF). Jornal do Brasil (in Brazilian Portuguese). 1986-11-05. p. 14. Archived (PDF) from the original on 2023-08-08. Retrieved 2023-08-08.
  4. ^ a b Dixit N, Patel C, Bhavsar M, Patel S, Rawal R, Solanki H (2022-05-02). "Quantitative Structure-activity Relationship (QSAR) study of Liver Toxic Drugs". International Association of Biologicals and Computational Digest. 1: 63–71. doi:10.56588/iabcd.v1i1.17. eISSN 2583-3995.
  5. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-03.
  6. ^ Pecknold JC, Ban TA, Lehmann HE, Climan M (June 1975). "Clomacran in the treatment of schizophrenic patients: a comparison of two assessment methods". International Journal of Clinical Pharmacology and Biopharmacy. 11 (4): 299–303. PMID 1099021.
  7. ^ "Clomacran". PubChem. U.S. National Library of Medicine. Retrieved 2023-08-25.
  8. ^ Andrews EB, Moore N, eds. (2014). Mann's Pharmacovigilance (1st ed.). Wiley. doi:10.1002/9781118820186. ISBN 978-0-470-67104-7.
  9. ^ Zirkle Charles L, U.S. patent 3,131,190 (1964 to Smith Kline French Lab).
  10. ^ E Anderson & H Graboyes, U.S. patent 3,781,358 (1973 to SmithKline Beecham Corp).
  11. ^ Elvin L Anderson & Harold Graboyes, U.S. patent 3,692,834 (1972 to Smith Kline and French Laboratories Ltd, GlaxoSmithKline LLC SmithKline Beecham Corp).
  12. ^ Elvin L Anderson & Harold Graboyes, U.S. patent 3,919,312 (1975 to SmithKline Beecham Corp).
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