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【结 构 式】 
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【药物名称】 【化学名称】(trans-Cyclohexane-1,2-diamine-kappaN,kappaN')(7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylato(2-)-kappaO2,kappaO3)platinum 【CA登记号】187819-79-0 (diastereomer), 233603-15-1 (diastereomer), 233603-16-2 (diastereomer), 233603-24-2 (diastereomer), 181297-04-1 (und 【 分 子 式 】C14H22N2O5Pt 【 分 子 量 】493.43184 |
【开发单位】Chinese Academy of Sciences (Originator), Chinese University of Hong Kong (Originator) 【药理作用】ONCOLYTIC DRUGS, Platinum Complexes, PP-2A Inhibitors |
合成路线1
The Diels-Alder cycloaddition between maleic anhydride (I) and furan (II) produced adduct (III). Subsequent double-bond hydrogenation in the presence of Pd/C furnished the saturated anhydride (IV).
| 【1】 Lin, G.; To, K.K.W.; Wang, X.; Han, X.; Au-Yeung, S.C.F.; Ho, Y.-P.; Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety. J Med Chem 2001, 44, 13, 2065. |
| 【2】 Ho, Y.P.; Au-Yeung, S.C.F.; Jiang, T.; Han, X.; Wang, X.; Lin, G.; Lu, S. (Chinese University of Hong Kong); Synthesis of platinum complexes and uses thereof. WO 9849174 . |
| 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) | 11182 | 2,5-Furandione; Maleic anhydride | 108-31-6 | C4H2O3 | 详情 | 详情 |
| (II) | 22372 | Furan | 110-00-9 | C4H4O | 详情 | 详情 |
| (III) | 49887 | exo-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride; exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride; 7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride | 6118-51-0 | C8H6O4 | 详情 | 详情 |
| (IV) | 49888 | 4,10-Dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C8H8O4 | 详情 | 详情 |
合成路线2
The platinum nitrate derivative (X) was prepared by two related procedures. Halogen-exchange of potassium tetrachloroplatinate (V) with KI produced the tetraiodoplatinate (VI), which was subsequently reacted with trans-1,2-diaminocyclohexane (VII) to give the diamino chelate (VIII). Alternatively, diamine (VII) was reacted with tetrachloroplatinate (V), yielding chelate (IX). Treatment of either iodo compound (VIII) or its analogous chloride (IX) with silver nitrate furnished the dinitrate compound (X). Finally, the diacid formed by basic hydrolysis of anhydride (IV) was in situ complexed with the platinum compound (X) to generate the title platinum complex.
| 【1】 Lin, G.; To, K.K.W.; Wang, X.; Han, X.; Au-Yeung, S.C.F.; Ho, Y.-P.; Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety. J Med Chem 2001, 44, 13, 2065. |
| 【2】 Ho, Y.P.; Au-Yeung, S.C.F.; Jiang, T.; Han, X.; Wang, X.; Lin, G.; Lu, S. (Chinese University of Hong Kong); Synthesis of platinum complexes and uses thereof. WO 9849174 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 49888 | 4,10-Dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C8H8O4 | 详情 | 详情 | |
| (V) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (VI) | 51694 | dipotassium tetraiodoplatinate(2-);potassium tetraiodoplatinate(II);Potassium tetraiodoplatinate | 14708-56-6 | I4K2Pt | 详情 | 详情 |
| (VII) | 11130 | (1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane | 20439-47-8 | C6H14N2 | 详情 | 详情 |
| (VIII) | 50042 | C6H14I2N2Pt | 详情 | 详情 | ||
| (IX) | 23063 | (R,R)-Cyclohexane-1,2-diamine dichloro platinum complex | C6H14Cl2N2Pt | 详情 | 详情 | |
| (X) | 19480 | (R,R)-Cyclohexane-1,2-diamine dinitrato platinum complex | n/a | C6H14N4O6Pt | 详情 | 详情 |