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【结 构 式】 
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【药物名称】 【化学名称】8(S)-(Bromomethyl)-6-(4-methoxycinnamoyl)-2-methyl-4-[N-[4-(piperidin-1-yl)piperidin-1-yl]carbamoyloxy]-3,6,7,8-tetrahydrobenzo[1,2-b:4,3-b']dipyrrole-1-carboxylic acid methyl ester hydrobromide 【CA登记号】 【 分 子 式 】C35H43Br2N5O6 【 分 子 量 】789.57086 |
【开发单位】Kyowa Hakko (Originator) 【药理作用】Oncolytic Drugs |
合成路线1
The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II), which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV). The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V), which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII). Finally, this compound is condensed with 4-(1-piperidinyl)piperidine-1-amine (VIII), and treated with HBr to furnish the target hydrobromide.
| 【1】 Amishiro, N.; Nagamura, S.; Saito, H.; Kobayashi, E.; Okamoto, A.; Gomi, K. (Kyowa Hakko Kogyo Co., Ltd.); DC-89 deriv.. EP 0702014; US 5670492; WO 9526964 . |
| 【2】 Nagamura, S.; Murakata, C.; Amishiro, N.; et al.; Synthesis and antitumor activity of duocarmycin derivatives: Modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups. Bioorg Med Chem 2000, 8, 2, 381. |
| 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) | 40881 | methyl (3bR,4aS)-2-methyl-8-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate | C26H25N3O7 | 详情 | 详情 | |
| (II) | 38365 | methyl (3bR,4aS)-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate | C14H14N2O3 | 详情 | 详情 | |
| (III) | 33752 | 4-nitrophenyl (E)-3-(4-methoxyphenyl)-2-propenoate | C16H13NO5 | 详情 | 详情 | |
| (IV) | 40882 | methyl (3bR,4aS)-6-[(E)-3-(4-methoxyphenyl)-2-propenoyl]-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate | C24H22N2O5 | 详情 | 详情 | |
| (V) | 40883 | methyl (8S)-8-(bromomethyl)-4-hydroxy-6-[(E)-3-(4-methoxyphenyl)-2-propenoyl]-2-methyl-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C24H23BrN2O5 | 详情 | 详情 | |
| (VI) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (VII) | 40884 | methyl (8S)-8-(bromomethyl)-6-[(E)-3-(4-methoxyphenyl)-2-propenoyl]-2-methyl-4-[[(4-nitrophenoxy)carbonyl]oxy]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C31H26BrN3O9 | 详情 | 详情 | |
| (VIII) | 40885 | C10H21N3 | 详情 | 详情 |