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【结 构 式】 
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【药物名称】Zeniplatin, CL-286558 【化学名称】cis-[2,2-Bis(aminomethyl)-1,3-propanediol-N,N'][1,1-cyclobutanedicarboxylato(2-)-O,O']platinum (II) 【CA登记号】111490-36-9 【 分 子 式 】C11H20N2O6Pt 【 分 子 量 】471.38185 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Oncolytic Drugs, Platinum Complexes |
合成路线1
Zeniplatin can be obtained by two related ways: 1) The reaction of dimethylsulfoxide with potassium tetrachloroplatinate (I) gives bis(dimethylsulfoxide-S,S')dichloroplatinum (II), which is then condensed with silver cyclobutane-1,1-dicarboxylate (III) in water to yield bis(dimethylsulfoxide-S,S')(1,1-cyclobutanedicarboxylato-O,O')platinum (IV). Finally, this compound is treated with 2,2-bis(aminomethyl)-1,3-propanediol (V) in refluxing water. 2) The reaction of potassium tetrachloroplatinate (I) with diamine (V) in water gives [2,2-bis(aminomethyl)-1,3-propanediol-N,N']dichloroplatinum (IV), which is treated with the silver salt (III) as before. The diamine (V) is prepared by reaction of 2,2-bis(bromomethyl)-1,3-propanediol (VII) with sodium azide in hot DMF to give 2,2-bis(azidomethyl)-1,3-propanediol (VIII), which is then reduced with hydrogen over Pt.
| 【1】 Grassing Child, R.; Bitha, P.; Hlavka, J.J.; Lin, Y. (Zyma); [2,2-Bis(aminomethyl)-1,3-propanediol-N,N']platinum complexes. AU 8432572; EP 0140830; ES 8802308; GB 2145720; JP 1985149581; US 4665202 . |
| 【2】 Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); Synthesis of cisplatinum analogs. EP 0296321 . |
| 【3】 Carvajal, S.G.; Citarella, R.V.; Bitha, P.; et al.; Water-soluble third generation antitumor Pt complexes, [2,2-bis(aminomethyl)-1,3-propanediol-N,N']- [1,1-cyclobutanedicarboxylato(2-)-O,O']Pt(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O']-[tetrahydro-4H-pyran-4,4-dimethanamine-N,N']Pt(II). J Med Chem 1989, 32, 8, 2015. |
| 【4】 Prous, J.; Castaner, J.; Zeniplatin. Drugs Fut 1992, 17, 6, 471. |
| 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) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (II) | 61657 | dichloroplatinum | Cl2Pt | 详情 | 详情 | |
| (III) | 12065 | Bis(dimethylsulfoxide-S,S')dichloroplatinum | C6H6Ag2O4 | 详情 | 详情 | |
| (IV) | 12069 | Cyclobutane-1,1-dicarboxylic acid platinum salt | C6H6O4Pt | 详情 | 详情 | |
| (V) | 12070 | 2,2-Bis(aminomethyl)-1,3-propanediol | C5H14N2O2 | 详情 | 详情 | |
| (VI) | 12071 | 2,2-Bis(hydroxymethyl)propane-1,3-diamine dichloro platinum complex | C5H14Cl2N2O2Pt | 详情 | 详情 | |
| (VII) | 12072 | Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol | 3296-90-0 | C5H10Br2O2 | 详情 | 详情 |
| (VIII) | 12073 | 2,2-Bis(azidomethyl)-1,3-propanediol | C5H10N6O2 | 详情 | 详情 |