Minaprine

Minaprine
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life2-2.5 hours
Identifiers
IUPAC name
  • 4-methyl-N-(2-morpholin-4-ylethyl)-6-phenylpyridazin-3-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.043.012
Chemical and physical data
FormulaC17H22N4O
Molar mass298.390 g·mol−1
3D model (JSmol)
SMILES
  • CC1=CC(=NN=C1NCCN2CCOCC2)C3=CC=CC=C3
InChI
  • InChI=1S/C17H22N4O/c1-14-13-16(15-5-3-2-4-6-15)19-20-17(14)18-7-8-21-9-11-22-12-10-21/h2-6,13H,7-12H2,1H3,(H,18,20) checkY
  • Key:LDMWSLGGVTVJPG-UHFFFAOYSA-N checkY

Minaprine (INN, USAN, BAN; brand names Brantur, Cantor) is a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsions.[2][3]

A study found that it acts as a reversible inhibitor of MAO-A (RIMA) in rats.[4] It has also been found to weakly inhibit acetylcholinesterase in rat brain (striatum) homogenates.[5]

It has demonstrated significant antibiotic activity against M. chelonae and M. abscessus in tests with antibiotic resistant bacteria.[6]

Synthesis

The first synthesis of minaprine was disclosed in patents published in 1979.[7]

The final step is the reaction between a chloro-substituted pyridazine and the primary amine group of a morpholine derivative.[7][8] The required pyridazine can be made by the reaction of acetophenone and pyruvic acid, followed by ring formation using hydrazine, giving a pyrazidinone. Treatment of this with phosphoryl chloride converts it to the required chloro derivative.[2]

References

  1. ^ 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 2023-08-16.
  2. ^ a b Wermuth CG, Schlewer G, Bourguignon JJ, Maghioros G, Bouchet MJ, Moire C, et al. (March 1989). "3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities". Journal of Medicinal Chemistry. 32 (3): 528–537. doi:10.1021/jm00123a004. PMID 2563772.
  3. ^ Fung M, Thornton A, Mybeck K, Wu JH, Hornbuckle K, Muniz E (1 January 2001). "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999". Therapeutic Innovation & Regulatory Science. 35 (1): 293–317. doi:10.1177/009286150103500134. S2CID 73036562.
  4. ^ Kan JP, Mouget-Goniot C, Worms P, Biziere K (March 1986). "Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat". Biochemical Pharmacology. 35 (6): 973–978. doi:10.1016/0006-2952(86)90085-7. PMID 3954800.
  5. ^ Contreras JM, Rival YM, Chayer S, Bourguignon JJ, Wermuth CG (February 1999). "Aminopyridazines as acetylcholinesterase inhibitors". Journal of Medicinal Chemistry. 42 (4): 730–741. doi:10.1021/jm981101z. PMID 10052979.
  6. ^ Chopra S, Matsuyama K, Hutson C, Madrid P (July 2011). "Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae". The Journal of Antimicrobial Chemotherapy. 66 (7): 1533–1536. doi:10.1093/jac/dkr154. PMID 21486854.
  7. ^ a b US patent 4169158, Henri Laborit, "Pyridazine derivatives in alleviating depressive states", issued 1979-09-25, assigned to CM Industries, SA 
  8. ^ "Minaprine". Pharmaceutical Substances. Thieme. Archived from the original on 2022-12-12. Retrieved 2024-07-21.
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