Minaprine

Minaprine

Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	N06AX07 ( WHO )
Legal status
Legal status	BR: Class C1 (Other controlled substances) [1] In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life	2-2.5 hours
Identifiers
IUPAC name 4-methyl-N-(2-morpholin-4-ylethyl)-6-phenylpyridazin-3-amine
CAS Number	25905-77-5  Y
PubChem CID	4199
ChemSpider	4054  Y
UNII	00U7GX0NLM
KEGG	D05039  Y
ChEMBL	ChEMBL278819  Y
CompTox Dashboard (EPA)	DTXSID5048477
ECHA InfoCard	100.043.012
Chemical and physical data
Formula	C17H22N4O
Molar mass	298.390 g·mol−1
3D model (JSmol)	Interactive image
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) Y Key:LDMWSLGGVTVJPG-UHFFFAOYSA-N Y

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a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsions.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. 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. USpatent 4169158,Henri Laborit,"Pyridazine derivatives in alleviating depressive states",issued 1979-09-25, assigned to CM Industries, SA 
8. "Minaprine". Pharmaceutical Substances. Thieme. Retrieved 2024-07-21.