Teniloxazine

Teniloxazine (Lucelan, Metatone), also known as sufoxazine and sulfoxazine, is a drug which is marketed in Japan.^[1] Though initially investigated as a neuroprotective and nootropic agent for the treatment of cerebrovascular insufficiency in the 1980s,^{[2][3][4][5][6][7][8][9]} it was ultimately developed and approved as an antidepressant instead.^[10] It acts as a potent norepinephrine reuptake inhibitor, with fair selectivity over the serotonin and dopamine transporters, and also behaves as an antagonist of the 5-HT_2A receptor.^[7][10][11]

Teniloxazine

Clinical data
Other names	Y-8894
Routes of administration	Oral
ATC code	None
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 2-{[2-(thiophen-2-ylmethyl)phenoxy]methyl}morpholine
CAS Number	62473-79-4 N 62473-80-7 (maleate)
PubChem CID	119114
ChemSpider	106426 Y
UNII	95Q6WNP25P
ChEMBL	ChEMBL2105438
CompTox Dashboard (EPA)	DTXSID10866932
Chemical and physical data
Formula	C16H19NO2S
Molar mass	289.39 g·mol−1
3D model (JSmol)	Interactive image
SMILES O1CCNCC1COc2ccccc2Cc3sccc3
InChI InChI=1S/C16H19NO2S/c1-2-6-16(19-12-14-11-17-7-8-18-14)13(4-1)10-15-5-3-9-20-15/h1-6,9,14,17H,7-8,10-12H2 Y Key:OILWWIVKIDXCIB-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Synthesis

ChemDrug Synthesis:^[12][13] Patents:^[14][15] Cerebrovascular dementia usage:^[16]

Amide formation between 1-(Benzylamino)-3-{2-[(thiophen-2-yl)methyl]phenoxy}propan-2-ol [62473-86-3] (1) and Chloroacetylchloride [79-04-9] (2) gives PC13682456 (3). In the presence of sodium metal closing of the ring morpholine occurs to give PC13682470 (4). Lactam reduction with lithium aluminium hydride affords 4-Benzyl-2-({2-[(thiophen-2-yl)methyl]phenoxy}methyl)morpholine [62473-77-2] (5). Treatment with Ethyl chloroformate [541-41-3] (6) gives the urethane and hence 4-Ethoxycarbonyl-2-[2-(2-thenyl)-phenoxymethyl]morpholine, PC21482171 (7). Hydrolysis of the carbamate in the presence of barium hydroxide completes the synthesis of Teniloxazine (8).

Alternately, base reaction between 1-[2-(2-thenyl)phenoxy]-2,3-epoxypropane [55506-46-2] (9) and 2-Aminoethyl hydrogen sulfate [926-39-6] (10) is another way to perform the synthesis.

See also

• Bifemelane
• Indeloxazine
• Viloxazine