Micheliolide derivative, and preparation method and use thereof

A technology of derivatives and lactones, which is applied in the field of medicine, can solve the problems that there are no reports on the treatment of inflammatory bowel disease with mimilactone and its derivatives, and achieve the improvement of colon shortening, the reduction of histopathological scores, and significant The effect of the therapeutic effect

CN108484550AActive Publication Date: 2018-09-04FOURTH MILITARY MEDICAL UNIVERSITY
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2018-09-04

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Abstract

The invention discloses a micheliolide derivative, and a preparation method and a use thereof. The derivative is obtained by chemically modifying micheliolide. Experiments show that the micheliolide derivative has a significant therapeutic effect on inflammatory bowel diseases, can be developed into anti-inflammatory drugs, especially can be developed into anti-inflammatory drugs for treating nonspecific intestinal inflammatory diseases, and has medicinal values. The micheliolide derivative is a compound having a structure represented by formula I, or a pharmaceutically acceptable salt, a tautomer, a stereoisomer or a precursor compound thereof.
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Description

technical field

[0001] The invention relates to a mimilactone derivative, a preparation method and application thereof, and belongs to the technical field of medicine. Background technique

[0002] Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease with two clinical subtypes, ulcerative colitis (UC) and Crohn's disease (CD). type. IBD is prone to occur in young and middle-aged people. The number of IBD patients in Europe is about 2.6 million to 3.7 million, and there are more than 1 million IBD patients in North America. In recent years, the incidence of IBD in my country is on the rise. When the disease is protracted, patients may develop complications such as intestinal perforation, obstruction, abdominal abscess, and even toxic megacolon, which seriously affect the quality of life of patients and cause great pain to patients. At present, clinical medicines for the treatment of IBD mainly include anti-inflammatory drugs (aminosali...

Examples

Embodiment Construction

[0049] The present invention will be further described below in conjunction with the accompanying drawings and examples. It should be understood that the examples are only for illustrating the present invention and are not intended to limit the scope of the present invention.

[0050] 1. Preparation of compound Ⅲ-8

[0051]

[0052] in N 2 Under protection, michelactone (99.2mg, 0.4mmol) and 5-fluorouracil (57.2mg, 0.44mmol) were added to a 25mL double-necked bottle, and then K 2 CO 3 (110.6 mg, 0.8 mmol). Then add 12mL THF (tetrahydrofuran) to the reaction system, stir overnight at room temperature, after TLC monitors the end of the reaction, filter, and the filtrate is concentrated under reduced pressure (circulating water type multi-purpose vacuum pump, 35° C.) to obtain the crude product, which can be used with petroleum A mixed solvent of ether:ethyl acetate=1:1 (volume ratio) was purified by column chromatography to obtain 147.5 mg (97.5%) of a colorless solid com...