Teniloxazine Explained

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]}

Synthesis

Amide formation between 1-(Benzylamino)-3-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-(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

Notes and References

1. Book: Ganellin CR, Triggle DJ, Macdonald F . Dictionary of pharmacological agents . 27 October 2011 . 1997 . CRC Press . 978-0-412-46630-4 . 1905.
2. Anami K, Yamamoto Y, Setoguchi M . [Pharmacological studies on sufoxazine (Y-8894). (I) Effects on experimental amnesia in mice] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 85 . 2 . 71–7 . February 1985 . 2859238 . 10.1254/fpj.85.71. free .
3. Izumi N, Yasuda H . [Pharmacological studies on sufoxazine (Y-8894). (II). Anti-anoxic effect] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 86 . 4 . 323–8 . October 1985 . 4085932 . 10.1254/fpj.86.323. free .
4. Usa T, Morimoto Y, Fukuda T, Anami K, Setoguchi M, Maruyama Y . [Pharmacological studies on Y-8894. (III). Its effect on the abnormal electrocorticogram induced by destruction of the internal capsule] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 88 . 4 . 289–97 . October 1986 . 3491778 . 10.1254/fpj.88.289. free .
5. Yasuda H, Izumi N, Nakanishi M, Anami K, Maruyama Y . [Pharmacological studies on Y-8894. (IV). Ameliorative effect on a cerebral energy metabolism disorder induced by KCN] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 88 . 5 . 363–7 . November 1986 . 3817653 . 10.1254/fpj.88.363. free .
6. Anami K, Yamamoto Y, Setoguchi M, Maruyama Y . [Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 89 . 3 . 145–53 . March 1987 . 2884174 . 10.1254/fpj.89.145. free .
7. Setoguchi M, Takehara S, Sakamori M, Anami K, Maruyama Y . [Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 90 . 1 . 41–9 . July 1987 . 2443434 . 10.1254/fpj.90.41. free .
8. Yasumatsu H, Yamamoto Y, Takamuku H, etal . [Pharmacological studies on Y-8894. (VII). Effects on transient cerebral ischemia-induced amnesia in rats] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 90 . 6 . 321–30 . December 1987 . 3443414 . 10.1254/fpj.90.321. free .
9. Anami K, Setoguchi M, Senoh H . [Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice] . ja . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 92 . 2 . 113–8 . August 1988 . 3224898 . 10.1254/fpj.92.113. free .
10. Ogura C, Kishimoto A, Kunimoto N, etal . Clinical pharmacology of a new antidepressant, Y-8894 in healthy young and elderly volunteers . British Journal of Clinical Pharmacology . 23 . 5 . 537–43 . May 1987 . 3593624 . 1386189 . 10.1111/j.1365-2125.1987.tb03089.x.
11. JP. 2008189616A . Therapeutic Agent for Attention-Deficit Hyperactivity Disorder .