A tegafur derivative containing 1,3,4-thiadiazole heterocycle and amide group

Abstract

The invention provides a tegafur derivative containing a 1,3,4-thiadiazole heterocyclic ring and an amide group. The structural formula of the tegafur derivative is as shown in the specification. A preparation method of the tegafur derivative comprises the steps of (1) dissolving a 3-(methoxycarbonylmethyl)tegafur in methanol, dropwise adding a sodium hydroxide solution, extracting by using ethyl acetate and distilled water and separating out an organic layer and a water layer, next, extracting by using ethyl acetate and blending the organic layers, and adding anhydrous sodium sulfate to obtain 1-(tetrahydro-2-furyl)-3-carbethoxy-5-fluoro-2,4-pyrimidinedione; (2) blending 1-(tetrahydro-2-furyl)-3-carbethoxy-5-fluoro-2,4-pyrimidinedione with dioxane, then adding sulfoxide chloride to obtain a 1-(tetrahydro-2-furyl)-3-chloracetyl-5-fluoro-2,4-pyrimidinedione solution, and then adding dioxane, evenly mixing and then sealing for later use; (3) taking 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole, dioxane and triethylamine, and dropwise adding the 1-(tetrahydro-2-furyl)-3-chloracetyl-5-fluoro-2,4-pyrimidinedione solution obtained in the step (2) to obtain a pure product 1-(tetrahydro-2-furyl)-3-acetamido-[5-p-nitrophenyl-(1,3,4-thiadiazole-2-yl)]-5-fluoro-2,4-pyrimidinedione. The tegafur derivative has anti-tumor effect and no obvious toxicity, and is used for clinically treating malignant tumors.

Description

technical field

[0001] The invention relates to a compound for inhibiting tumor cell proliferation, which is a tegafur derivative containing 1,3,4-thiadiazole heterocycle and amide group. Background technique

[0002] Since the incidence of malignant tumors is increasing year by year, drugs to inhibit tumors have become one of the important topics studied by technicians from all over the world. Among various tumor-inhibiting compounds, 5-fluorouracil (5-Fu) is a relatively effective and safe compound, which is widely used in the treatment of various cancers. After years of clinical drug statistics, it shows that although it inhibits the proliferation of tumor cells by interfering with and blocking the synthesis of DNA, RNA and protein, 5-Fu has a short half-life and can only be administered intravenously or arterially. relatively bigger. For this reason, those skilled in the art have been studying a tegafur derivative containing 1,3,4-thiadiazole heterocycle and amide grou...

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