Medical use of andrographolidume and its derivatives and analogs

Abstract

This invention relates to the following general expression compound or the medicine use of its prodrug. Concretely it relates to the general expression compound or its prodrug's use in preparing TNF-alphaand / or IL-1beta inhibitor. R1 stands for hydrogen, alkyl, aryl, cyclic hydrocarbon or heterocyclic hydrocarbon. R2 stands for the following chemical formula, R' stands for hydrogen, alkyl, aryl, hetero aryl, alkoxy, halogen group, amido or hydroxy group, R'' stands for hydrogen, alkyl, cyclic hydrocarbon, aryl, hetero aryl, alkoxy, halogen group or amido.

Description

technical field [0001] The present invention relates to the medical use of andrographolide and its derivatives and analogs, in particular to andrographolide and its derivatives, analogs and their pharmaceutically acceptable salts and prodrugs in the preparation of TNF- and / or IL-1β inhibitory use in pharmaceuticals. Background technique [0002] Inflammation is the body's defense-based response to the damage caused by various inflammatory factors. The local manifestations of inflammation are redness, swelling, heat, pain and dysfunction. These manifestations are more obvious in acute body surface inflammation, but less obvious in visceral inflammation and chronic inflammation. Inflammation is not only local, but also often causes systemic reactions. Common systemic reactions include fever, increased leukocyte count in the blood, and varying degrees of degeneration and necrosis of heart, liver, kidney and other solid organs. [0003] According to pathological classificatio...

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Problems solved by technology

However, the test method described in this article has the following problems: 1) The division response of PBMC after being stimulated by PHA is very strong, and the amount of TNFa in the medium will increase significantly, but the article does not point out the increase of TNFa caused by PHA stimulation 2) The purpose and design of the test have nothing to do with the currently recognized models of human and animal autoimmune diseases; 3) The high concentration of cells in the test was cultured for three days, and the state of the cultured cells was unknown; the medium may have been exhausted; the TNFa product The kinetic changes of the TNFa are not clear; and the peak of TNFa is known to be produced within 24 hours; 4) The experimental error is too large, so the experimental conclusion is in doubt

Although the researchers speculated that andrographolide has an effect on the downstream factors of the inflammatory pathological process, they did not reveal the direct inhibitory effect of andrographolide on the upstream precursor inflammatory factor TNF-α

[0010] In addition, the latest research has confirmed that neoandrographolide, a derivative (or analogue) of andrographolide, is more effective in treating bacillary dysentery than chloramphenicol and furazolidone (research on the anticancer effect of andrographolide http: / / www.hkhk666.com / lunwen / ); 14-deoxyandrographolide and neoandrographolide can inhibit mouse paw swelling caused by egg white and inflammatory response caused by croton oil (Deng, W.L, et al.Chin. Pharm.Bull.17, 185-188) and has the effect of inducing cancer cell differentiation (Matsuda, T et al., Chem.Pharm.Bull.42, 1216-1225), but the article did not mention the above two compounds Is it effective in animal models of rheumatoid arthritis and ulcerative colitis?

[0011] In the existing literature, there is no report about the activity of andrographolide and its derivatives and analogs to inhibit the expression of TNF-α and IL-1β

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