|
【结 构 式】 
|
【药物名称】ALS-007 【化学名称】12-(beta-D-Glucopyranosyl)-3,9-dihydroxy-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione 【CA登记号】 【 分 子 式 】C26H21N3O9 【 分 子 量 】519.47197 |
【开发单位】Advanced Life Sciences (Originator) 【药理作用】ONCOLYTIC DRUGS, DNA Topoisomerase I Inhibitors |
合成路线1
Condensation of the magnesium iodide salt of 5-(benzyloxy)indole (I) with N-(benzyloxymethyl)-3,4-dibromomaleimide (II) provided the monoindolyl maleimide (III). Coupling of (III) with the benzyl-protected glucose (IV) via Mitsunobu reaction afforded the glycosylated indole (V). A second indolyl group was then introduced in (V) to give the bisindolylmaleimide (VI), which was oxidatively cyclized to the indolocarbazole (VII) using palladium bis(trifluoroacetate). Finally, hydrogenolysis of the benzyl protecting groups of (VII) over Pd/C furnished the title compound.
| 【1】 Lineswala, J.P.; Kuffel, M.J.; Zhang, H.; Aytes, S.A.; Zembower, D.E.; Ames, M.M.; Indolocarbazole poisons of human topoisomerase I: Regioisomeric analogues of ED-110. Bioorg Med Chem Lett 1999, 9, 2, 145. |
| 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) | 30840 | 5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole | 1215-59-4 | C15H13NO | 详情 | 详情 |
| (II) | 30841 | 1-[(benzyloxy)methyl]-3,4-dibromo-1H-pyrrole-2,5-dione | C12H9Br2NO3 | 详情 | 详情 | |
| (III) | 30842 | 3-[5-(benzyloxy)-1H-indol-3-yl]-1-[(benzyloxy)methyl]-4-bromo-1H-pyrrole-2,5-dione | C27H21BrN2O4 | 详情 | 详情 | |
| (IV) | 30843 | (2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-ol | C34H36O6 | 详情 | 详情 | |
| (V) | 30844 | 1-[(benzyloxy)methyl]-3-(5-(benzyloxy)-1-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-1H-indol-3-yl)-4-bromo-1H-pyrrole-2,5-dione | C61H55BrN2O9 | 详情 | 详情 | |
| (VI) | 30845 | 3-[5-(benzyloxy)-1H-indol-3-yl]-1-[(benzyloxy)methyl]-4-(5-(benzyloxy)-1-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-1H-indol-3-yl)-1H-pyrrole-2,5-dione | C76H67N3O10 | 详情 | 详情 | |
| (VII) | 30846 | 3,9-bis(benzyloxy)-6-[(benzyloxy)methyl]-12-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione | C76H65N3O10 | 详情 | 详情 |