Synthesis of benzsulfamide HDAC (Histone Deacetylase) inhibitor and application of benzsulfamide HDAC inhibitor in resisting tumor

Abstract

The invention relates to a chemical method for synthesizing a benzsulfamide HDAC (Histone Deacetylase) inhibitor by taking paratoluensulfonyl chloride and ortho-nitroaniline as materials. The method comprises the following steps: (1), synthesis of a toluene sulfonamide compound, wherein the paratoluensulfonyl chloride and ortho-nitroaniline are condensed at a high temperature by taking pyridine as a solvent to obtain the toluene sulfonamide compound; (2), synthesis of a primary amine compound, wherein bromination is carried out on methyl of a benzene ring by NBS (N-Bromosuccinimide) under action of AIBN (2,2-Azobisisobutyronitrile), sodium azide is used to convert the methyl into an azide, and then dehydrated into the primary amine compound under action of triphenylphosphine; (3), synthesis of an amino compound, wherein 3-hydroxymethylpyridine and the primary amine compound are condensed to obtain nitryl compound containing sulfamide under action of CDI (Carbonyldiimidazole), and stannous chloride is used to reduce the nitryl compound to obtain the amino compound. An activity test indicates the compounds have tumor cell proliferation resistance equivalent to that of a positive drug MS-275, and have potential of being developed into anti-tumor drugs.

Description

Technical field: [0001] The invention belongs to the field of drug synthesis, and relates to a chemical synthesis method of a benzenesulfonamide histone deacetylase inhibitor and its application in antitumor. Background technique: [0002] Histone deacetylases (Histone deacetylases, HDACs) are one of the most studied tumor-related molecular targets in recent years, and are closely related to the occurrence, development and metastasis of tumors and the angiogenesis of tumor tissues. Histone deacetylase inhibitors (Histone deacetylase inhibitors, HDACIs) are anti-tumor drugs developed by targeting HDACs, they can cause cell cycle blockade and tumor cell selective apoptosis, in vitro and in vivo All have obvious antitumor effect. So far, two HDACs inhibitors (SAHA and FK228) have been approved by the US Food and Drug Administration (FDA) for the treatment of cutaneous T-cell lymphoma. Therefore, the development of high-efficiency, low-toxicity, and strong selectivity HDACs in...

AI Technical Summary

Problems solved by technology

In the functional region of MS-275, benzamide plays an important role in the binding of zinc ions, and the transformation of the functional region has gradually attracted the attention of medicinal chemists. However, no information about replacing benzamide with benzenesulfonate has been found Synthesis and Application of Amide Compounds

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