-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-[5-[(E)-2-Cyano-2-(N,N-diethylcarbamoyl)vinyl]-2-hydroxy-3-nitrophenoxycarbonyl]-3-hydroxy-L-tyrosine methyl ester

【CA登记号】

【分子式】C₂₅H₂₆N₄O₁₀

【分子量】542.50677

【开发单位】Finncovery (Originator), University of Kuopio (Originator)

【药理作用】Antiparkinsonian Drugs, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, COMT Inhibitors, Dopamine Precursors

合成路线1

Esterification of L-Dopa (I) with thionyl chloride in methanol leads to the methyl ester (II). The phenolic hydroxyls of (II) are further acylated by acetyl chloride in trifluoroacetic acid to produce diacetate (III). Treatment of the protected derivative of L-Dopa (III) with diphosgene gives rise to isocyanate (IV). This is then coupled to entacapone (V) in refluxing acetonitrile to furnish carbamate (VI). The acetate ester groups of (VI) are finally removed by treatment with 3N HCl in acetone.

参考文献中间体

【1】 Leppanen, J.; et al.; Design and synthesis of a novel L-dopa-entacapone codrug. J Med Chem 2002, 45, 6, 1379.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	15272	(2S)-2-amino-3-(3,4-dihydroxyphenyl)propionic acid; 3-hydroxy-L-tyrosine; Levodopa	59-92-7	C₉H₁₁NO₄	详情	详情
(II)	29568	methyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate		C₁₀H₁₃NO₄	详情	详情
(III)	61955	methyl (2S)-2-amino-3-[3,4-bis(acetyloxy)phenyl]propanoate		C₁₄H₁₇NO₆	详情	详情
(IV)	61956	methyl (2S)-3-[3,4-bis(acetyloxy)phenyl]-2-isocyanatopropanoate		C₁₅H₁₅NO₇	详情	详情
(V)	61957	(E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide		C₁₄H₁₅N₃O₅	详情	详情
(VI)	61958	methyl (2S)-3-[3,4-bis(acetyloxy)phenyl]-2-[({5-[(E)-2-cyano-3-(diethylamino)-3-oxo-1-propenyl]-2-hydroxy-3-nitrophenoxy}carbonyl)amino]propanoate		C₂₉H₃₀N₄O₁₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)