O-aminobenzoic acid sulfonylation derivative as well as preparation method and application thereof

Abstract

The invention relates to an o-aminobenzoic acid sulfonylation derivative as well as a preparation method and application thereof. The structure of the derivative is shown as a general formula (I), wherein R1 and R2 can be same or different and are respectively and independently selected from H, alkyl, hydroxyl, CF3, halogen, amino, nitryl, hydroxamino, alkoxy or phenyl; or when being substituted on adjacent carbon atoms, the R1 and the R2 are together with the connected carbon atoms to form benzene ring or methylenedioxy substituent group; R3 is selected from the alkyl, alkoxy, heteroaryl, naphthenic base, substituted or not substituted aryl; R4 and R5 can be same or different and are respectively and independently selected from H, C1-C6 alkyl, hydroxyl, C1-C6 alkoxy, the halogen or the nitryl; or the R4 and R5 are substituted on adjacent positions on the ring to jointly form methylenedioxy or ethylenedioxy; and the R6 is H, the C1-C6 alkyl or the C1-C6 alkoxy. The compound disclosed by the invention can be used for the third generation tumour multidrug resistance inhibitors and can be individually or jointly applied or combined with an excipient to be applied to the treatment of diseases such as cancers and the like when serving as a P-glycoprotein regulator.

Description

technical field [0001] The invention relates to a sulfonylated anthranilic acid derivative and its preparation method and application, in particular to the application of a sulfonylated anthranilic acid derivative in multi-drug resistance inhibitors, and belongs to the field of medicinal chemistry. Background technique [0002] The most important problem in cancer chemotherapy is that tumor cells are prone to multidrug resistance (MDR). Tumor multidrug resistance refers to the phenomenon that tumor cells are simultaneously resistant to anticancer drugs with completely different chemical structures, targets and mechanisms of action, and is the main reason for the failure of cancer chemotherapy. According to reports, almost all drugs currently in use can treat some cancers. However, due to the strong multidrug resistance of tumors, chemotherapy often fails. According to statistics from the American Cancer Society, in the annual mortality rate of cancer, more than 90% of cance...

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Problems solved by technology

However, these compounds lack sufficient specificity and affinity for P-gp, thus causing many toxic side effects, such as related to cardiovascular system side effects

The second-generation inhibitors are similar in structure to the first-generation inhibitors, and have higher selectivity and lower toxicity. For example, Valspodar, Biricodar and XR9051 are 3 to 100 times more active than the first-generation inhibitors. Drugs can significantly change the plasma pharmacokinetics of anticancer drugs used at the same time, making it difficult to determine a safe and effective dosage clinically, and also affect the normal P-glycoprotein efflux, thus limiting its clinical application. application on

So far, the documents disclosed at home and abroad have not reported the compounds involved in the present invention and their uses

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