【结 构 式】 |
【药物名称】 【化学名称】(5R,5aR,8aS,9S)-9-[4-(1H-Benzimidazol-2-yl)phenylamino]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one 【CA登记号】 【 分 子 式 】C34H29N3O7 【 分 子 量 】591.62613 |
【开发单位】Genelabs (Originator) 【药理作用】ONCOLYTIC DRUGS, DNA Topoisomerase II Inhibitors, DNA-Intercalating Drugs, Epipodophyllotoxins |
合成路线1
Oxidative oxidation of p-nitrobenzaldehyde (I) and 1,2-phenylenediamine (II) in DMF in the presence of nitrobenzene produced benzimidazole (III). Subsequent reduction of the nitro group of (III) by means of NaBH4 and CuCl afforded aniline (IV). Bromide (VI) was prepared by treatment of 4'-demethyl epipodophyllotoxin (V) with HBr. The title compound was then obtained by coupling aniline (IV) with bromide (VI) using BaCO3 in 1,2-dichloroethane.
【1】 Cheng, H.-H.; Guan, J.; Zhu, X.-K.; Cheng, Y.-C.; Tachibana, Y.; Bastow, K.F.; Lee, K.-H.; Gurwith, M.; Cho, S.J.; Antitumor agents. 194. Synthesis and biological evaluations of 4-beta-mono-, -di-, and -trisubstituted aniline-4'-O-demethyl-podophyllotoxin and related compounds with improved pharmacological profiles. J Med Chem 1999, 42, 13, 2441. |
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) | 18184 | 4-Nitrobenzaldehyde | 555-16-8 | C7H5NO3 | 详情 | 详情 |
(II) | 12824 | 2-Aminophenylamine; o-Phenylenediamine; 1,2-Benzenediamine | 95-54-5 | C6H8N2 | 详情 | 详情 |
(III) | 33735 | 2-(4-nitrophenyl)-1H-benzimidazole | C13H9N3O2 | 详情 | 详情 | |
(IV) | 33736 | 4-(1H-benzimidazol-2-yl)aniline; 4-(1H-benzimidazol-2-yl)phenylamine | C13H11N3 | 详情 | 详情 | |
(V) | 13053 | (5R,5aR,8aR,9S)-9-Hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | 6559-91-7 | C21H20O8 | 详情 | 详情 |
(VI) | 14609 | (5R,5aR,8aR,9S)-9-bromo-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C21H19BrO7 | 详情 | 详情 |