TNP-470, AGM-1470, -Drug Synthesis Database

【结构式】

【药物名称】TNP-470, AGM-1470

【化学名称】6-O-(Chloroacetylcarbamoyl)fumagillol
　　　　　　[3R,4S(1R,2R),5S,6R]-6-(Chloroacetylcarbamoyloxy)-4-(1,2-epoxy-1,5-dimethyl-4-hexenyl)-5-methoxy-1-oxaspiro[2.5]octane
　　　　　　[3R-[3alpha,4alpha(2R,3R),5beta,6beta]-N-Chloroacetylcarbamic acid 5-methoxy-4-[2-methyl-3-(3-methyl-2-butenyl)oxyranyl]-1-oxaspiro[2.5]octan-6-yl ester

【CA登记号】129298-91-5

【分子式】C₁₉H₂₈ClNO₆

【分子量】401.89111

【开发单位】Takeda (Originator), TAP (Codevelopment)

【药理作用】Leukemia Therapy, Lymphoma Therapy, Oncolytic Drugs, Prostate Cancer Therapy, Renal Cancer Therapy, Solid Tumors Therapy, Angiogenesis Inhibitors, Methionine Aminopeptidase-2 Inhibitors

合成路线1

By condensation of fumagillol [(3R,4S,5S,6R)-4-(1,2-epoxy-1,5-dimethyl4-hexenyl)-6-hydroxy-5-methoxy-1-oxaspiro[2.5]octane] (I) with chloroacetylisocyanate (II) by means of dimethylaminopyridine (DMAP) in dichloromethane.

参考文献中间体

【1】 Fujita, T.; Kanamaru, T.; Folkman, M.; Ingber, D. (Children's Med. Cent. Corp.; Takeda Chemical Industries, Ltd.); Angiogenesis inhibitory agent. EP 0357061 .
【2】 Kishimoto, S.; Fujita, T. (Takeda Chemical Industries, Ltd.); Fumagillol derivs. EP 0359036; EP 0682020; JP 1991007270; US 5164410; US 5166172; US 5180738; US 5698586 .
【3】 Kishimoto, S.; Marui, S.; Fujita, T. (Takeda Chemical Industries, Ltd.); Cyclohexanol derivs., production and use thereof. EP 0415294; JP 1991279376; US 5180735 .
【4】 Marui, S.; Itoh, F.; Kozai, Y.; Sudo, K.; Kishimoto, S.; Chemical modification of fumagillin. I. 6-O-Acyl, 6-O-sulfonyl, 6-O-alkyl, and 6-O-(N-substituted-carbamoyl)fumagillols. Chem Pharm Bull 1992, 40, 1, 96-101.
【5】 Mealy, N.; Prous, J.; Castaner, J.; AGM-1470. Drugs Fut 1994, 19, 11, 981.

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)	13712	(3R,4S,5S,6R)-5-Methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-2-butenyl)oxiranyl]-1-oxaspiro[2.5]octan-6-ol		C₁₆H₂₆O₄	详情	详情
(II)	13713	2-Chloroacetyl isocyanate	4461-30-7	C₃H₂ClNO₂	详情	详情

Extended Information