Nelarabine, Nelzarabine, GW-506U78, GW-506U, 506U78, 506U, Atriance, -Drug Synthesis Database

【结构式】

【药物名称】Nelarabine, Nelzarabine, GW-506U78, GW-506U, 506U78, 506U, Atriance

【化学名称】9-(beta-D-Arabinofuranosyl)-6-methoxy-9H-purin-2-amine
　　　　　　9-beta-D-Arabinofuranosyl-6-O-methylguanine

【CA登记号】121032-29-9

【分子式】C₁₁H₁₅N₅O₅

【分子量】297.2727

【开发单位】GlaxoSmithKline (Originator)

【药理作用】Leukemia Therapy, Lymphoma Therapy, Oncolytic Drugs, Antimetabolites

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

参考文献中间体

【1】 Krmitsky TA. 1988. Antiviral compounds. EP 0294114[本专利为GlaxoSmithKline (GB)所有]

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)	11996	1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione; Uridine	58-96-8	C₉H₁₂N₂O₆	详情	详情
(II)	66535	(2R,3S,3aS,9aR)-3-hydroxy-2-(hydroxymethyl)-3,3a-dihydro-2H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-6(9aH)-one		C₉H₁₀N₂O₅	详情	详情
(III)	38235	1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione		C₉H₁₂N₂O₆	详情	详情

合成路线2

参考文献中间体

【1】 Herbal K,Kitteringham J.Voyle M.et al. 2005.Synthesis af the enantiomer of nelarabine. Tetrahedron Lett, 46 (17): 2961～2964

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)	66537	(2S,5S)-5-(hydroxymethyl)tetrahydrofuran-2,3,4-triol		C₅H₁₀O₅	详情	详情
(II)	66536	(2R,5S)-5-(acetoxymethyl)tetrahydrofuran-2,3,4-triyl triacetate		C₁₃H₁₈O₉	详情	详情
(III)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(IV)	66538	(2R)-2-(acetoxymethyl)-5-(2-amino-6-methoxy-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate		C₁₇H₂₁N₅O₈	详情	详情

合成路线3

参考文献中间体

【1】 Janeba Z,Lin XY, Robinsw.et aL 2004.FUnctionalization of guanosine and 2'-deoxyguanosine at C6:a modified appel process and SNAr displacement of imidazole. Nucl Acid, 23(1&2): 137～147
【2】 Nair V, Lyons AG. 1990. Hypoxanthine nucleoside counterparts of the antibiotic, cordycepin.Tetrahedron. 46 (23): 7677一7692

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)	66539	2-amino-9-((3aS,6S,6aS)-6-(hydroxymethyl)-2,2,3a,6a-tetramethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3H-purin-6(9H)-one		C₁₅H₂₁N₅O₅	详情	详情
(II)	66540	9-((3aS,6S,6aS)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2,3a,6a-tetramethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2-(tritylamino)-3H-purin-6(9H)-one		C₄₀H₄₉N₅O₅Si	详情	详情
(III)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(IV)	66541	(2S,3R)-5-(2-amino-6-(1H-imidazol-1-yl)-9H-purin-9-yl)-4-(hydroxymethyl)tetrahydrofuran-2,3-diol		C₁₃H₁₅N₇O₄	详情	详情

合成路线4

The reaction of 6-chloropurine-2-amine (I) with methanol and NaH gives 6-O-methylguanine (II), which is mixed with uracil arabinoside (III), purine nucleoside phosphorylase and uridine phosphorylase and submitted to incubation in a potassium phosphate solution at 37 C. After 26 days of incubation, the target compound is isolated.

参考文献中间体

【1】 Krenitsky, T.A.; Koszalka, G.W.; Jones, L.A.; Averett, D.R.; Moorman, A.R. (Glaxo Wellcome plc); Antiviral cpds.. AU 8816718; EP 0294114; JP 1988310831; US 5424295; US 5539098 .

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)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(II)	38234	6-methoxy-9H-purin-2-amine; 6-methoxy-9H-purin-2-ylamine	20535-83-5	C₆H₇N₅O	详情	详情
(III)	38235	1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione		C₉H₁₂N₂O₆	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)