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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-{methyl}morpholine
CAS Number	62473-79-4 62473-80-7 (maleate)
PubChem CID	119114
ChemSpider	106426
UNII	95Q6WNP25P
ChEMBL	ChEMBL2105438
CompTox Dashboard (EPA)	DTXSID10866932
Chemical and physical data
Formula	C16H19NO2S
Molar mass	289.39 g·mol
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 Key:OILWWIVKIDXCIB-UHFFFAOYSA-N
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Teniloxazine (Lucelan, Metatone), also known as sufoxazine and sulfoxazine, is a drug which is marketed in Japan. Though initially investigated as a neuroprotective and nootropic agent for the treatment of cerebrovascular insufficiency in the 1980s, it was ultimately developed and approved as an antidepressant instead. 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.

Synthesis

Amide formation between 1-(Benzylamino)-3-{2-phenoxy}propan-2-ol (1) and Chloroacetylchloride (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-phenoxy}methyl)morpholine (5). Treatment with Ethyl chloroformate (6) gives the urethane and hence 4-Ethoxycarbonyl-2-morpholine, PC21482171 (7). Hydrolysis of the carbamate in the presence of barium hydroxide completes the synthesis of Teniloxazine (8).

Alternately, base reaction between 1--2,3-epoxypropane (9) and 2-Aminoethyl hydrogen sulfate (10) is another way to perform the synthesis.

See also

• Bifemelane
• Indeloxazine
• Viloxazine

References

1. Ganellin CR, Triggle DJ, Macdonald F (1997). Dictionary of pharmacological agents. CRC Press. p. 1905. ISBN 978-0-412-46630-4. Retrieved 27 October 2011.
2. Anami K, Yamamoto Y, Setoguchi M (February 1985). "[Pharmacological studies on sufoxazine (Y-8894). (I) Effects on experimental amnesia in mice]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 85 (2): 71–7. doi:10.1254/fpj.85.71. PMID 2859238.
3. Izumi N, Yasuda H (October 1985). "[Pharmacological studies on sufoxazine (Y-8894). (II). Anti-anoxic effect]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 86 (4): 323–8. doi:10.1254/fpj.86.323. PMID 4085932.
4. Usa T, Morimoto Y, Fukuda T, Anami K, Setoguchi M, Maruyama Y (October 1986). "[Pharmacological studies on Y-8894. (III). Its effect on the abnormal electrocorticogram induced by destruction of the internal capsule]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 88 (4): 289–97. doi:10.1254/fpj.88.289. PMID 3491778.
5. Yasuda H, Izumi N, Nakanishi M, Anami K, Maruyama Y (November 1986). "[Pharmacological studies on Y-8894. (IV). Ameliorative effect on a cerebral energy metabolism disorder induced by KCN]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 88 (5): 363–7. doi:10.1254/fpj.88.363. PMID 3817653.
6. Anami K, Yamamoto Y, Setoguchi M, Maruyama Y (March 1987). "[Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 89 (3): 145–53. doi:10.1254/fpj.89.145. PMID 2884174.
7. ^ Setoguchi M, Takehara S, Sakamori M, Anami K, Maruyama Y (July 1987). "[Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 90 (1): 41–9. doi:10.1254/fpj.90.41. PMID 2443434.
8. Yasumatsu H, Yamamoto Y, Takamuku H, et al. (December 1987). "[Pharmacological studies on Y-8894. (VII). Effects on transient cerebral ischemia-induced amnesia in rats]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 90 (6): 321–30. doi:10.1254/fpj.90.321. PMID 3443414.
9. Anami K, Setoguchi M, Senoh H (August 1988). "[Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 92 (2): 113–8. doi:10.1254/fpj.92.113. PMID 3224898.
10. ^ Ogura C, Kishimoto A, Kunimoto N, et al. (May 1987). "Clinical pharmacology of a new antidepressant, Y-8894 in healthy young and elderly volunteers". British Journal of Clinical Pharmacology. 23 (5): 537–43. doi:10.1111/j.1365-2125.1987.tb03089.x. PMC 1386189. PMID 3593624.
11. JP 2008189616A, "Therapeutic Agent for Attention-Deficit Hyperactivity Disorder" 
12. Serradell, MN; Blancafort, P.; Castaer, J.; Y-8894. Drugs Fut 1981, 6, 7, 423.
13. Muro, Tomio; Yuki, Hiroshi; Kawakita, Takeshi; Chihara, Yasuaki; Yasumoto, Mitsuyoshi; Setoguchi, Shinro; Anami, Koretake; Setoguchi, Michihide (1986). "Syntheses and Pharmacological Activities of 2-(Substituted Phenoxymethyl) morpholine Derivatives". YAKUGAKU ZASSHI. 106 (9): 764–774. doi:10.1248/yakushi1947.106.9_764.
14. Tomio Muro, et al. U.S. patent 4,005,084 (1977 to Welfide Corp).
15. Muro Tomio, Chihara Yasuaki, et al. DE2530860, (1977 to Yoshitomi Pharmaceutical).
16. Michihide Setoguchi, Koretake Anami, & Hiroshi Yasuda, EP0193637 (1986 to Welfide Corp).

• Drugs not assigned an ATC code
• Antidepressants
• Morpholines
• Thiophenes
• Phenol ethers