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【结 构 式】 
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【药物名称】 【化学名称】2,3-Dimethoxy-6-propyl-12H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinolin-6-ium chloride 【CA登记号】 【 分 子 式 】C22H22ClNO4 【 分 子 量 】399.87794 |
【开发单位】National Cancer Institute (Originator), Purdue University (Originator) 【药理作用】Oncolytic Drugs, DNA Topoisomerase I Inhibitors, DNA-Intercalating Drugs |
合成路线1
Isoquinoline (III) was prepared by the condensation of piperonal N-propylimine (I) with 4,5-dimethoxyhomophthalic anhydride (II). Subsequent intramolecular Friedel-Crafts acylation of (III) in the presence of Eaton's reagent gave rise to the indenoisoquinoline (IV). Reduction of the ketone and lactam functions of (IV) using borane-tetrahydrofuran complex provided alcohol (V). This underwent simultaneous dehydration and dehydrogenation in the presence of Pd/C in refluxing HOAc to afford, after treatment with NaCl, the target indenoisoquinolinium chloride salt.
| 【1】 Jayaraman, M.; Fox, B.M.; Hollingshead, M.; Kohlhagen, G.; Pommier, Y.; Cushman, M.; Synthesis of new dihydroindeno[1,2-c]isoquinoline and indenoisoquinolinium chloride topoisomerase I inhibitor having high in vivo anticancer activity in the hollow fiber animal model. J Med Chem 2002, 45, 1, 242. |
| 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) | 55161 | N-[(E)-1,3-benzodioxol-5-ylmethylidene]-N-propylamine; N-[(E)-1,3-benzodioxol-5-ylmethylidene]-1-propanamine | C11H13NO2 | 详情 | 详情 | |
| (II) | 55162 | 6,7-dimethoxy-1H-isochromene-1,3(4H)-dione | C11H10O5 | 详情 | 详情 | |
| (III) | 55163 | (3S,4R)-3-(1,3-benzodioxol-5-yl)-6,7-dimethoxy-1-oxo-2-propyl-1,2,3,4-tetrahydro-4-isoquinolinecarboxylic acid | C22H23NO7 | 详情 | 详情 | |
| (IV) | 55164 | (6aS,12aR)-2,3-dimethoxy-6-propyl-6a,12a-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | C22H21NO6 | 详情 | 详情 | |
| (V) | 55165 | (6aS,12R,12aR)-2,3-dimethoxy-6-propyl-6,6a,12,12a-tetrahydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinolin-12-ol | C22H25NO5 | 详情 | 详情 |