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2,3,4-trihydroxybenzenesulfonamide derivatives as well as preparation method and application thereof

A technology for trihydroxybenzenesulfonamide and derivatives, which is applied in the field of 2,3,4-trihydroxybenzenesulfonamide derivatives and their preparation, and can solve the problems of less research and the like

Active Publication Date: 2018-07-20
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there are no effective small molecule inhibitors acting on the IL-17A-IL-17RA signaling pathway, and there are very few related studies. As of 2017, there are only two documents (reference: Med.Chem.Commun. ,2016,7,2344–2348; Scientific Reports,2016,6,30859) reported compounds can inhibit IL-17A, so it is urgent to develop small molecule inhibitors of IL-17A to broaden clinical drug options

Method used

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  • 2,3,4-trihydroxybenzenesulfonamide derivatives as well as preparation method and application thereof
  • 2,3,4-trihydroxybenzenesulfonamide derivatives as well as preparation method and application thereof
  • 2,3,4-trihydroxybenzenesulfonamide derivatives as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Preparation of N,N'-(1,4-phenylene)bis(2,3,4-trihydroxy-5-(N-propylsulfonamide)benzamide)(lyz003-81)

[0028]

[0029] Under cooling in an ice-water bath, 20 mL of chlorosulfonic acid (3.496 g, 30 mmol, 15.0 eq) in DCM was added dropwise to 5 mL of compound 1 (424 mg, 2 mmol, 1.0 eq) in DCM, after the addition was complete, stir at room temperature for 4 h , and then heated to 75 ° C, reflux 4h. Cool to room temperature, quench with ice water, extract with DCM, and spin dry the obtained reaction product 2. 2mL of n-propylamine (221.7mg, 3.75mmol, 2.5eq) in DCM was added dropwise to 6mL of compound 2 (466mg, 1.5mmol, 1.0eq) in DCM, after the addition was complete, it was stirred at room temperature, and the reaction was detected by TLC. The product was separated by column chromatography as the raw material for the next reaction. The above compound (406.7mg, 1.22mmol, 2.4eq) and EDC (233.9mg, 1.22mmol, 2.4eq) in anhydrous DCM (8mL) were stirred at room temperature fo...

Embodiment 2

[0032] Preparation of N,N'-(1,4-phenylene)bis(2,3,4-trihydroxy-5-(N-isobutylsulfonamide)benzamide)(lyz003-175)

[0033]

[0034] The preparation method was as in Example 1, prepared from compound 2 (800mg, 2.57mmol), isobutylamine (564.6mg, 7.72mmol), p-phenylenediamine (48.7mg, 0.45mmol). Yellow-white solid with a yield of 91%.

[0035] 1 H NMR (400MHz, DMSO-d 6 )δ12.94(brs,1H),10.60(s,1H),8.04(s,1H),7.66(s,2H),6.93(s,1H),2.57–2.54(m,2H),1.69–1.60 (m,1H),0.79(d,J=6.6,6H). 13 CNMR (100MHz, DMSO-d 6 )δ167.69, 153.46, 147.73, 134.06, 133.36, 122.10, 120.01, 118.31, 107.01, 50.09, 27.85, 20.00, 19.89.

Embodiment 3

[0037] Preparation of N,N'-(1,4-phenylene)bis(2,3,4-trihydroxy-5-(N-4-butyric acid methyl sulfonamide)benzamide)(lyz003-194)

[0038]

[0039] The preparation method was as in Example 1, prepared from compound 2 (800mg, 2.57mmol), methyl 3-aminobutyrate hydrochloride (1.18g, 7.72mmol), p-phenylenediamine (48.7mg, 0.45mmol). Yellow-white solid with a yield of 67%.

[0040] 1 H NMR (400MHz, DMSO-d 6 )δ13.04(brs,1H),10.63(s,1H),8.05(s,1H),7.67(d,J=3.2,2H),3.93(s,1H),3.53(s,3H),2.83 –2.76(s,2H),2.36–2.26(m,2H),1.69–1.56(m,2H). 13 C NMR (100MHz, DMSO-d 6 )δ174.62,174.59,173.51,173.48,168.32,167.51,154.88,154.11,148.68,148.37,139.73,134.59,133.88,124.66,122.60,122.47,120.59,119.75,118.74,111.60,110.00,107.38,51.71,51.69,42.39 ,42.22,31.20,30.76,25.12,25.00.

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Abstract

The invention discloses 2,3,4-trihydroxybenzenesulfonamide derivatives as well as a preparation method and an application thereof. The specific structure is shown in formula (I). In the formula (I), most of 2,3,4-trihydroxybenzenesulfonamide derivatives show good IL-17 (interleukin-17)A resistance activity. The IL-17A is related with autoimmune diseases and also related with occurrence and development of cancer. On the basis, the 2,3,4-trihydroxybenzenesulfonamide derivatives can be used for preparing immunoregulation drugs.

Description

technical field [0001] The invention belongs to the field of organic synthesis and medicine, and relates to a class of 2,3,4-trihydroxybenzenesulfonamide derivatives, a preparation method thereof and an application in immune regulation. Background technique [0002] The interleukin-17 (IL-17) family of cytokines includes six members: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. IL-17 family cytokines play an important role in the body's innate immunity and acquired immune system. This family of cytokines can promote the body's resistance to infection by various pathogens, and is closely related to the occurrence and development of autoimmune diseases and tumors. relevant. Currently IL-17A is the most well-studied member of this family, mainly composed of CD4 + Secreted by T cell subset Th17 (T helper 17) cells. Blocking antibodies against IL-17A and its receptors have achieved good results in clinical trials of autoimmune diseases such as psoriasis and rheumatoid ar...

Claims

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Application Information

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IPC IPC(8): C07C311/29C07C303/40C07D209/16A61K31/18A61K31/4045A61P37/02A61P35/00
Inventor 王巍
Owner WUHAN UNIV
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