305 results about "Genotoxicity" patented technology

The invention relates to an antitumor 3,5-diphenylmethylene-4-piperidone derivative and a preparation method thereof, and belongs to the technical fields of antitumor drugs and preparation methods thereof. The preparation method comprises the following steps: performing a Claisen-Schmidt condensation reaction on a 4-piperidone derivative having antitumor activity and 4-trifluoromethyl through 4-piperidone hydrochloride to obtain an intermediate a; and reacting the intermediate a with an acylation or sulfonylation reagent to obtain N-R-3,5-di(4-trifluoromethyl benzylidene)-4-piperidone b-5. The 3,5-diphenylmethylene-4-piperidone derivative is novel in structure, has the advantage of combination of a plurality of molecular targets, and has multidrug resistance activity; and the genotoxicity of currently-used antitumor drugs can be avoided. Compared with normal cells, the derivative has higher antitumor activity to tumor cells, so that the derivative has a great application prospect in the field of antitumor drugs.

The invention discloses a preparation method for free-state edoxaban.The synthetic route is shown in the description.According to the preparation method, the charging sequence is changed, and a curing problem caused by a traditional method is reduced; according to an existing method, a starting material A and triethylamine are added at first, a starting material B is added, a large amount of solid will appear in the temperature increasing process, and the stirring uniformity is greatly affected, so that the yield is greatly lowered, and the method is adopted for greatly solving the problem and improving the yield; when the compound free-state edoxaban is synthetized, a first amount of a saturated sodium bicarbonate water solution is added at first, the phenomenon that a product is rapidly separated out and impurities are included due to the fact that the added saturated sodium bicarbonate water solution is excessive is avoided, and meanwhile introduction of genotoxicity impurity methanesulfonate is effectively avoided; after the impurities are completely hydrolyzed, a second amount of the saturated sodium bicarbonate water solution is added so that the product can be separated out thoroughly; the method improves the crystallization way, the yield is improved, and generation of impurities is reduced.