A compound with quinolinone tetravalent platinum structure, preparation method and application thereof in the preparation of antitumor drugs
A compound, tetravalent platinum technology, applied in the direction of antineoplastic drugs, platinum-based organic compounds, platinum-group organic compounds, etc., can solve problems such as low absorption rate, strong toxic and side effects, and serious drug resistance
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[0063] The preparation method of the above compound is as follows:
[0064] (1) The reaction formula of the asymmetric monoquoquinolinone tetramiplatin compound 1 of the formula 1 is as follows:
[0065]
[0066] Among them, the compound molar ratio of Compound 4, Compound 5, TBTU, and Triethylamine is 1: (1.0-1.3): (1.0-1.3): The relationship between compound 4 and DMF is 1 g: (30) -80ml);
[0067] (2) The reaction type of the symmetric double-substituted quinolinone tetramiplatin compound 2 is as follows:
[0068]
[0069] Among them, the compound molar ratio of Compound 4a, Compound 5, TBTU, and Triethylamine is 1: (2.2 ~ 3): (2.2 to 3): (2.2 to 3), the relationship between compound 4 and DMF is 1 g: (30 ~ 80ml).
[0070] Further, the method of preparing a non-symmetric monoquoquinolinone tetramic platinum compound is as follows:
[0071] The TBTU and quinolinone derivative 5 were added to the reaction vessel, and the air in a nitrogen gas changing system was added, and the...
Embodiment 1
[0091] Example 1: Preparation of quinolinone tetramiplatin compounds shown in Formulas 1 and 2
[0092] 1. Synthesis of dihydroxy-dioxin (IV) 4A-1
[0093]
[0094] To 250 ml round bottom flask, cisplatin 1.0 g, 30 mL of distilled water, stirred, and slowly add concentration of 30% hydrogen oxygen to 50 ml of a concentration of 30%, and the temperature to 60 ° C was stirred in the reaction system. The reaction was stopped, and the crystalline was placed in -4 ° C for 12 hours, the filtration was separated to obtain a yellow solid, adding an appropriate amount of distilled water, heating to 80 ° C, adding 4 ° C for 12 hours, filtered the compound 4A-1 yellow crystal (0.82g 74%).
[0095] 2. Synthesis of Hydroxychloro Osulatin (IV) 4A-2
[0096]
[0097] To the 250 ml round bottom flask, Osli platinum 1.0 g, distilled water was 30 mL, stirred, and the concentration was slowly added dropwise to 50 ml of hydrogen peroxide at a reaction system, and the temperature to 60 ° C was sti...
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