sirt6 small molecule agonist and its application

A technology of agonists and small molecules, applied in medical preparations containing active ingredients, organic active ingredients, metabolic diseases, etc., can solve problems such as no drug reports

Active Publication Date: 2022-04-05
上海宇道生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Up-regulation of SIRT6 activity is considered to be one of the new strategies for the treatment of the above-mentioned diseases. Therefore, the discovery of SIRT6 small molecule agonists has become a hot spot of major international pharmaceutical companies and research institutes, but there are no reports of related drugs yet

Method used

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  • sirt6 small molecule agonist and its application
  • sirt6 small molecule agonist and its application
  • sirt6 small molecule agonist and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1. Preparation of SIRT6 small molecule agonists

[0032] method one

[0033]

[0034] Method Two

[0035]

[0036] Specific implementation method 1:

[0037]

[0038] Take a round bottom flask of appropriate size, and dissolve the aniline compound (1) in an appropriate amount of pyridine solution at room temperature. Then add 1.2 times the equivalent of p-nitrobenzenesulfonyl chloride (2) at the same temperature, and after stirring at room temperature for 10 minutes, raise the reaction temperature to 75° C. for more than 8 hours. After TLC monitors that the reaction is complete, cool the reaction to room temperature, add 2 mol / mL hydrochloric acid, adjust the pH to 3-4, then add ethyl acetate to extract 3 times, combine the organic phases, and wash 3 times with saturated brine. Dry over anhydrous sodium sulfate. After the ethyl acetate solution was distilled under reduced pressure, the obtained residual substances, namely different substitution substa...

example 1

[0065] Example 1 (001)

[0066] 2-Chloro-nitrogen-(4-(nitrogen-(3-chloro-2-methylphenyl)sulfamoyl)phenyl)benzenesulfonamide

[0067] LCMS (ESI) m / z: 471.0 (M+H) +

example 2

[0068] Example 2 (002)

[0069] 2-Bromo-nitrogen-(4-(nitrogen-(3-chloro-2-methylphenyl)sulfamoyl)phenyl)benzenesulfonamide

[0070] LCMS (ESI) m / z: 514.9 (M+H) +

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Abstract

The invention discloses a SIRT6 small molecule agonist and an application thereof. The agonist is a tricyclic bissulfonamide derivative represented by formula (1) or a pharmacologically acceptable salt thereof, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 The same or different, represents hydrogen atom, halogen, said halogen refers to fluorine, chlorine, bromine and iodine, hydroxyl, nitro, amino, carboxyl, acid ester, sulfonamide, mercapto, methoxy, ethoxy, benzyloxy base, methyl, tert-butyl, cyano; R 11 Represents a hydrogen atom, chlorine, nitro, amino, benzyl alcohol, benzyl chloride, benzylamine, carboxyl, and acid ester. The three rings are connected by amide bonds. The invention designs and synthesizes a high-efficiency and low-toxicity SIRT6 small molecule agonist, which can obviously stimulate the activity of SIRT6 in an in vitro experiment, and is of great significance to the development of drugs for related diseases.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a small molecule agonist of SIRT6 and its application as a pharmaceutical compound to prevent or treat related diseases. Background technique [0002] The mammalian Sirtuin family contains 7 members (SIRT1-7), which generally have mono-ADP-ribosylation (Mono-ADP-ribosylation) enzyme activity, or deacylation (Deacylation) enzyme activity, the latter mainly including deacetylation (Deacetylation), demyristoylation (Demyristoylation), etc.; they are widely involved in various life processes, such as energy metabolism, cellular stress, genome stability, aging, and tumors. SIRT6 is one of the main members of the Sirtuin family, with a large Rossmann fold domain and a small zinc ion domain in its spatial structure, in which the cofactor NAD of the enzyme + Both the substrate polypeptide and the substrate polypeptide are combined in the Rossmann domain, and the zinc ion domain has a ...

Claims

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Application Information

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Patent Type & AuthorityPatents(China)
IPC IPC(8): C07C311/44C07C317/14A61K31/63A61P35/00A61P3/10
CPCA61K31/63C07C311/44C07C317/14
Inventor张健黄志敏陈颖毅
Owner上海宇道生物技术有限公司