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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 a...

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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 potentnorepinephrine reuptake inhibitor, with fair selectivity over the serotonin and dopaminetransporters, 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. ↑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 (febrero de 1985). " [ Estudios farmacológicos sobre la sufoxazina (Y-8894). (I) Efectos sobre la amnesia experimental en ratones ] " . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (en japonés). 85 (2): 71– 7. doi : 10.1254/fpj.85.71 . PMID 2859238 . 
  3. ^ Izumi N, Yasuda H (octubre de 1985). « [ Estudios farmacológicos sobre la sufoxazina (Y-8894). (II). Efecto antianóxico ] » . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (en japonés). 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 (octubre de 1986). " [ Estudios farmacológicos sobre Y-8894. (III). Su efecto sobre el electrocorticograma anormal inducido por la destrucción de la cápsula interna ] " . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (en japonés). 88 (4): 289– 97. doi : 10.1254/fpj.88.289 . PMID 3491778 . 
  5. ↑ Yasuda H, Izumi N, Nakanishi M, Anami K, Maruyama Y (noviembre de 1986). " [ Estudios farmacológicos sobre Y-8894. (IV). Efecto beneficioso sobre un trastorno del metabolismo energético cerebral inducido por KCN ] " . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (en japonés). 88 (5): 363– 7. doi : 10.1254/fpj.88.363 . PMID 3817653 . 
  6. ↑ Anami K, Yamamoto Y, Setoguchi M, Maruyama Y (marzo de 1987). " [ Estudios farmacológicos sobre Y-8894. (V) Efecto sobre el aprendizaje y la memoria en ratas intactas y experimentalmente amnésicas ] " . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (en japonés). 89 (3): 145– 53. doi : 10.1254/fpj.89.145 . PMID 2884174 . 
  7. 12Setoguchi 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. 12Ogura 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).