Curcumin derivative and application of curcumin derivative as cannabinoid receptor modulator

Abstract

The invention relates to the preparation of a curcumin derivative and application of the curcumin derivative as a cannabinoid receptor modulator. In the synthetic route of the curcumin derivative, 10% of Pd-C is used for reducing the curcumin; for protecting a phenolic hydroxyl group, only 2.0% mol of DMAP (Dimethylaminopyridine) is used for catalysis and (Boc)2O of which the mole amount is 2.05 times as much as that of the curcumin is used so that reaction is completely realized; during a Mannich reaction, Mannich reagents such as N,N,N',N'-tetramethyldiaminomethane prepared in advance are used so as to avoid that an acid component reacts with formaldehyde to generate by-products at first. In the whole route, the target compound is obtained through reducing, protection, alkylation, deprotection and the Mannich reaction with the curcumin as the raw material. The route has the characteristics of cheap and available raw material, high yield and easy operation. The curcumin derivative is capable of inhibiting the hepatic stellate cells of a hepatic fibrosis rat from synthesizing and secreting extracellular matrix through a cannabinoid receptor, promoting the degradation of the extracellular matrix, reducing the deposition of the extracellular matrix in the liver and further developing the effect of treating the hepatic fibrosis.

Description

technical field [0001] The invention relates to the preparation of curcumin derivatives and their application as cannabinoid receptor modulators, in particular to the effect of curcumin derivatives in the preparation of anti-fibrosis drugs. technical background [0002] Hepatic fibrosis (Hepatic Fibrosis, HF) is a compensatory response in the tissue repair process secondary to various forms of chronic liver injury, and it is also a necessary pathological process for the development of chronic liver disease to cirrhosis. Hepatic stellate cells (HSCs) are the main source of extracellular matrix proteins in chronic liver diseases. When liver fibrosis occurs, HSCs are abnormally activated and proliferated, and synthesize and secrete a large amount of extracellular matrix (Extracellular matrix, ECM), which eventually leads to excessive deposition of ECM. During liver injury, HSC undergo a phenotypic shift, acquiring myofibroblast characteristics, increased collagen synthesis and...

AI Technical Summary

Problems solved by technology

However, further studies have found that curcumin has low activity in the body, less absorption in the body, fast metabolism, and low bioavailability, which greatly limits its application.

However, curcumin's exact biological activity and relatively simple molecular structure are still excellent lead compounds for structural modification and drug screening for liver disease treatment.

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