Taltirelin, TA-0910, Ceredist, -Drug Synthesis Database

【结构式】

【药物名称】Taltirelin, TA-0910, Ceredist

【化学名称】(S)-1-Methyl-4,5-dihydroorotyl-L-histidyl-L-prolinamide
　　　　　　(S)-N-[(1-Methyl-2,6-dioxohexahydropyrimidin-4-yl)carbonyl]-L-histidyl-L-prolinamide

【CA登记号】103300-74-9

【分子式】C₁₇H₂₃N₇O₅

【分子量】405.41676

【开发单位】Tanabe Seiyaku (Orphan Drug), Tanabe Seiyaku (Originator)

【药理作用】Neurodegenerative Diseases, Treatment of, NEUROLOGIC DRUGS, TRH Analogs

合成路线1

The methylation of 4,5-dihydroorotic acid benzyl ester (I) with methyl iodide gives the corresponding 1-methyl derivative (II), which is debenzylated by hydrogenolysis with H2 over Pd/C yielding (S)-1-methyl-4,5-dihydroorotic acid (III). Finally, this compound is condensed with L-histidyl-L-prolinamide (IV) by means of dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (HONSU) in DMF.

参考文献中间体

【1】 Sugano, H.; Ishida, R.; Yamamura, M. (Tanabe Seiyaku Co., Ltd.); Dihydroorotic acid derivs. and process for their preparation. JP 1986033197 .
【2】 Sugano, H.; Ishida, R.; Yamamura, M. (Tanabe Seiyaku Co., Ltd.); Dihydroorotic acid derivs., process for their preparing and pharmaceutical compsn. containing them. EP 0168042; ES 8705463; ES 8707738; ES 8800208; US 4665056 .
【3】 Sugano, H.; Ishida, R.; Yamamura, M. (Tanabe Seiyaku Co., Ltd.); Therapeutic agent for central nervous system disorders. JP 1987234029 .
【4】 Prous, J.; Castaner, J.; TA-0910. Drugs Fut 1991, 16, 2, 127.
【5】 Suzuki, M.; Sugano, H.; Matsumoto, K.; Yamamura, M.; Ishida, R.; Synthesis and central nervous system actions of thyrotropin-releasing hormone analogues containing a dihydroorotic acid moiety. J Med Chem 1990, 33, 8, 2130-37.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	31250	benzyl (4S)-2,6-dioxohexahydro-4-pyrimidinecarboxylate	C₁₂H₁₂N₂O₄	详情	详情
(II)	31251	benzyl (4S)-1-methyl-2,6-dioxohexahydro-4-pyrimidinecarboxylate	C₁₃H₁₄N₂O₄	详情	详情
(III)	31252	(4S)-1-methyl-2,6-dioxohexahydro-4-pyrimidinecarboxylic acid	C₆H₈N₂O₄	详情	详情
(IV)	31253	(2S)-1-[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]-2-pyrrolidinecarboxamide	C₁₁H₁₇N₅O₂	详情	详情

Extended Information