Dazepinil

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

Clinical data
Other names	HRP 543
Identifiers
IUPAC name 2,3-dimethyl-4-phenyl-4,5-dihydro-1,3-benzodiazepine
CAS Number	75991-50-3 75241-19-9
PubChem CID	53432
ChemSpider	48264
UNII	730EPY2HSM
ChEMBL	ChEMBL117042
CompTox Dashboard (EPA)	DTXSID20996719
Chemical and physical data
Formula	C17H18N2
Molar mass	250.345 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=NC2=CC=CC=C2CC(N1C)C3=CC=CC=C3
InChI InChI=1S/C17H18N2/c1-13-18-16-11-7-6-10-15(16)12-17(19(13)2)14-8-4-3-5-9-14/h3-11,17H,12H2,1-2H3 Key:STDYWHYUOSSCBO-UHFFFAOYSA-N

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

The chemical synthesis has been reported:^[2][3]

Dazepinil synthesis

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

1. 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.
2. 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.
3. 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.
4. "PC20452101". PubChem. U.S. National Library of Medicine.
5. "PC10857157". PubChem. U.S. National Library of Medicine.