Application of chalcone compound containing carboxymethyl rhodanine structure

Abstract

The invention relates to an application of a chalcone compound containing a carboxymethyl rhodanine structure shown in a general formula (I) or a pharmaceutically acceptable salt as a PTP1B inhibitorin preparation of a medicine for preventing, delaying or treating diseases mediated by PTP1B. The general formula (I) is shown in the description, wherein R1 is C1-C6 alkoxy, C1-C6 alkyl, substitutedbenzyloxy, H, halogen, NO2, NH2, OH, SH and CN; R2 is H, C1-8 alkyl and aralkyl; n is 1-10; and A and B-rings are benzene ring, naphthalene ring, aryl, heteroaryl and heterocycloalkyl, and each groupis optionally and independently substituted by 1, 2 or 3 groups such as halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C4 halogenated alkyl, C1-C4 halogenated alkoxy, NO2, NH2, NH(C1-C6)alkyl and N(C1-C6)alkyl(C1-C6)alkyl. The compound has high affinity and inhibitory activity to PTP1B, mainly exists in the form of acid in organisms, and is favorable for penetrating cell membranes and improving bioavailability.

Description

technical field [0001] The invention belongs to the application field of chalcone compounds containing carboxymethyl rhodanine structure, in particular to chalcone compounds containing carboxymethyl rhodanine structure or pharmaceutically acceptable salts thereof as PTP1B inhibitors. Application in medicines for preventing, delaying or treating diseases mediated by PTP1B. Background technique [0002] Type II diabetes is a common metabolic disorder, characterized by peripheral insulin resistance, and at the molecular level, it is manifested as a loss of signal transduction after insulin binds to insulin receptors. The phosphorylation level of protein tyrosine is an important regulator of intracellular signal transduction, which is jointly regulated by protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP). Recent studies have found that protein tyrosine phosphatase 1B can specifically hydrolyze the phosphate group on phosphorylated tyrosine in proteins, and pl...

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Problems solved by technology

[0009] The object of the present invention is to provide a kind of application of the chalcone compound containing carboxymethylrhodanine structure or its pharmaceutically acceptable salt as shown in general formula (I), specifically as PTP1B inhibitor, in the preparation Application in medicines for preventing, delaying or treating diseases mediated by PTP1B, especially in the preparation of medicines for treating and / or preventing type II diabetes and obesity, to solve the problem that existing PTP1B inhibitor compounds themselves have relatively High negative charge, mainly exists in the form of negative ions in the body, which is not conducive to permeating the cell membrane, resulting in poor bioavailability, and poor selectivity to different PTPases, which is not conducive to the technology of effectively acting on specific PTPase targets problem;

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