Chemistry:Teniloxazine

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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-HT2A receptor.[7][10][11]

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

References

  1. ↑ Dictionary of pharmacological agents. CRC Press. 1997. pp. 1905. ISBN 978-0-412-46630-4. https://books.google.com/books?id=A0THacd46ZsC&pg=PA1905. Retrieved 27 October 2011. 
  2. ↑ "[Pharmacological studies on sufoxazine (Y-8894). (I) Effects on experimental amnesia in mice]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 85 (2): 71–7. February 1985. doi:10.1254/fpj.85.71. PMID 2859238. 
  3. ↑ "[Pharmacological studies on sufoxazine (Y-8894). (II). Anti-anoxic effect]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 86 (4): 323–8. October 1985. doi:10.1254/fpj.86.323. PMID 4085932. 
  4. ↑ "[Pharmacological studies on Y-8894. (III). Its effect on the abnormal electrocorticogram induced by destruction of the internal capsule]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 88 (4): 289–97. October 1986. doi:10.1254/fpj.88.289. PMID 3491778. 
  5. ↑ "[Pharmacological studies on Y-8894. (IV). Ameliorative effect on a cerebral energy metabolism disorder induced by KCN]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 88 (5): 363–7. November 1986. doi:10.1254/fpj.88.363. PMID 3817653. 
  6. ↑ "[Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 89 (3): 145–53. March 1987. doi:10.1254/fpj.89.145. PMID 2884174. 
  7. ↑ 7.0 7.1 "[Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 90 (1): 41–9. July 1987. doi:10.1254/fpj.90.41. PMID 2443434. 
  8. ↑ "[Pharmacological studies on Y-8894. (VII). Effects on transient cerebral ischemia-induced amnesia in rats]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 90 (6): 321–30. December 1987. doi:10.1254/fpj.90.321. PMID 3443414. 
  9. ↑ "[Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 92 (2): 113–8. August 1988. doi:10.1254/fpj.92.113. PMID 3224898. 
  10. ↑ 10.0 10.1 "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. doi:10.1111/j.1365-2125.1987.tb03089.x. PMID 3593624. 
  11. ↑ "Therapeutic Agent for Attention-Deficit Hyperactivity Disorder" JP patent 2008189616A
  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).



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