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【结 构 式】 
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【药物名称】Bisnafide mesylate, Bisnafide mesilate, NSC-D640430, DMP-840 【化学名称】(R,R)-2,2'-(Ethane-1,2-diyl)bis[imino(1-methylethane-2,1-diyl)]bis(5-nitro-2,3-dihydro-1H-benzo[de]isoquinoline-1,3-dione) dimethanesulfonate 【CA登记号】145124-30-7, 144849-63-8 (free base) 【 分 子 式 】C34H36N6O14S2 【 分 子 量 】816.82582 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Oncolytic Drugs, DNA-Intercalating Drugs |
合成路线1
The condensation of tert-butoxycarbonyl-D-alanine (I) with ethylenediamine (II) gives the corresponding protected diamide (III), which is deprotected in acidic medium to the diamide (IV). The reduction of (IV) with diborane in THF yields the (R,R)-4,7-diazadecane-2,9-diamine (V), which is finally condensed with 3-nitronaphthalene-1,8-dicarboxylic acid anhydride (VI) in refluxing ethanol and salified with methanesulfonic acid.
| 【1】 Robinson, C.P.; Robinson, K.A.; Castaner, J.; Bisnafide Mesylate. Drugs Fut 1996, 21, 3, 239. |
| 【2】 Sun, J.-H. (DuPont Pharmaceuticals Co.); Bis-naphthalimides containing amino-acid derived linkers as anticancer agents. EP 0506008; EP 0577753; JP 1994506229; US 5206249; WO 9217453 . |
| 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) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
| (II) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (III) | 15861 | tert-butyl N-[(1R,8R)-1,8,12,12-tetramethyl-2,7,10-trioxo-11-oxa-3,6,9-triazatridec-1-yl]carbamate | C18H34N4O6 | 详情 | 详情 | |
| (IV) | 15862 | (2R)-2-amino-N-(2-[[(2R)-2-aminopropanoyl]amino]ethyl)propanamide | C8H18N4O2 | 详情 | 详情 | |
| (V) | 15863 | (2R)-N(1)-(2-[[(2R)-2-aminopropyl]amino]ethyl)-1,2-propanediamine; N-[(2R)-2-aminopropyl]-N-(2-[[(2R)-2-aminopropyl]amino]ethyl)amine | C8H22N4 | 详情 | 详情 | |
| (VI) | 15864 | 5-nitro-1H,3H-benzo[de]isochromene-1,3-dione; 3-Nitro-1,8-naphthalic anhydride | 3027-38-1 | C12H5NO5 | 详情 | 详情 |