Dazepinil
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| Other names | HRP 543 |
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| Chemical and physical data | |
| Formula | C17H18N2 |
| Molar mass | 250.345 g·mol−1 |
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Dazepinil, classified as a tricyclic antidepressant, is a pharmacological compound that has never been approved for medical use. Its mechanism of action involves inhibiting the reuptake of norepinephrine and serotonin at the synaptic cleft, thereby enhancing neurotransmitter availability in the brain.
Dazepinil is a 1,3-benzodiazepine derivative that has been reported to have marked anti-tetrabenazine activity, to inhibit neurotransmitter uptake into rat brain synaptosomes and to lack anticholinergic activity as evidenced by negligible displacement of [3H]quinuclidinyl benzylate from rat brain muscarinic receptors, and by negligible antagonism of the cholinergic stimulation produced by physostigmine or oxotremorine. This suggests that HRP 534 might be clinically useful as a novel antidepressant which is devoid of anticholinergic side-effects.[1]
Synthesis
[edit]The chemical synthesis has been reported:[2][3]
The base catalyzed reaction between N-Boc-o-toluidine [74965-31-4] (1) and N-Benzylidenemethylamine [622-29-7] (2) gives PC20452101.[4] The removal of the Boc protecting group by treatment with trifluoroacetic acid afforded 2-[2-(Methylamino)-2-phenylethyl]aniline, PC10857157 (3).[5] Reaction of the resulting diamine with methyl orthoacetate adds the required extra carbon atom and leads to the formation of dazepinil (4).
References
[edit]- ^ Ankier SI (1986). "Progress in Medicinal Chemistry". 4 Recent Progress in the Development of New Antidepressant Drugs. Progress in Medicinal Chemistry. Vol. 23. Elsevier. pp. 121–185. doi:10.1016/S0079-6468(08)70342-4. ISBN 978-0-444-80802-8. PMID 3310107.
- ^ Geyer HM, Martin LL, Crichlow CA, Dekow FW, Ellis DB, Kruse H, et al. (April 1982). "(+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 1. Synthesis and evaluation of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and analogues as potential antidepressant agents". Journal of Medicinal Chemistry. 25 (4): 340–346. doi:10.1021/jm00346a003. PMID 7200144.
- ^ Martin LL, Setescak LL, Worm M, Crichlow CA, Geyer HM, Wilker JC (April 1982). "(+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 2. Nuclear-substituted analogues of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and (+/-)-4,5-dihydro-2-ethyl-3-methyl-4-phenyl-3H-1,3-benzodiazepine as potential antidepressant agents". Journal of Medicinal Chemistry. 25 (4): 346–351. doi:10.1021/jm00346a004. PMID 7069712.
- ^ "PC20452101". PubChem. U.S. National Library of Medicine.
- ^ "PC10857157". PubChem. U.S. National Library of Medicine.