STAT3 small-molecule inhibitor and its application

A small molecule inhibitor and inhibitor technology, applied in the field of tumor drugs, can solve the problems of incomplete inhibition, poor cell permeability, limited inhibitory activity, etc.

Active Publication Date: 2014-06-25
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

However, peptide inhibitors have poor cell permeability, easy metabolism, and poor bioavailability. Kinase inhibitors cannot completely inhibit the activity of the downstream STAT3 pathway, while non-peptide small molecule inhibitors have li

Method used

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  • STAT3 small-molecule inhibitor and its application
  • STAT3 small-molecule inhibitor and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1. Preparation of compound general formula (2a)

[0031]

[0032] General formula (2a) is a specific compound type of general formula (1) and general formula (1a). Since part B can be a ring or chain structure, it is represented by R in general formula (2a).

[0033]

[0034] Substituted or unsubstituted benzene rings, heterocycles, cinnamic acids or aliphatic acids are refluxed in anhydrous ethanol-concentrated sulfuric acid (20:1) solution for 9 hours, spin to dry 2 / 3 of the solvent, and add an appropriate amount of crushed ice to the residue , then NaHCO 3 The pH of the solution was adjusted to neutral, and the product was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain a colorless liquid, namely product 3. Dissolve the ester obtained above in absolute ethanol, add an equivalent amount of hydrazine hydrate, and reflux for 24 hours. Spin off part of...

preparation approach 1

[0042]

preparation approach 2

[0044]

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PUM

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Abstract

The invention discloses a STAT3 small-molecule inhibitor and its application, and the STAT3 inhibitor takes an N'-(1-(2,4 dihydroxy phenyl)ethylidene) benzoyl hydrazine derivative or its pharmacologically acceptable salt shown in a formula (1) or a formula (1a) as an effective component. In the formula, R1 and R2 on A ring can be hydroxyl, methoxy carboxyl and ester, and B can be an annular or a chain state. The STAT3 small-molecule inhibitor has selectivity and high activity, According to a three-grade structural design, biosynthesis and reconstructing optimization of STAT3, then a fluorescence polarization method and a CCK-8 method are employed for detecting activity and researching the mechanism on inhibition of tumor cells growth and promotion of differentiation apoptosis, so that effect of the STAT3 small-molecule inhibitor on prevention and control of tumor formation and tumor treatment can be described.

Description

technical field [0001] The invention relates to the field of tumor drugs, in particular to an active small molecule inhibitor designed according to the tertiary structure of signal transduction and transcription factor 3 (STAT3). Background technique [0002] Signal transducer and transcription factor 3 (STAT3) belongs to the STATs family. There are seven members of this family, STAT1-STAT7, which are encoded by different genes, among which STAT1, STAT3, and STAT5 are highly homologous. The STATs family is stimulated by cell growth factors such as EGFR, IL-6, PDGF, etc. to undergo tyrosine phosphorylation to mediate physiological functions such as cell growth, differentiation, migration, and apoptosis. Studies have shown that excess phosphorylated STAT3 can be detected in prostate cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, and myeloma, while the level of phosphorylated STAT3 in normal epithelial cells is significantly lower. [0003] STAT3 consis...

Claims

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Application Information

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IPC IPC(8): C07C251/86C07C249/16C07C311/16C07C303/40C07C317/44C07C315/04C07C319/20C07C323/62C07D307/85C07D333/38C07D231/12C07D233/64C07D213/54C07D295/088C07D295/155C07D295/192C07D285/06C07D213/78C07D249/04C07D209/42C07D471/04C07D307/68C07D307/24C07D261/18C07D333/70C07D409/04C07D333/68C07D487/04C07D207/48C07D207/34C07D401/04C07D231/16C07D231/14C07D231/56C07D231/18C07D231/38C07D405/04C07D265/06C07D277/56C07D417/04C07D241/24C07D241/26C07D241/44C07D239/28C07D239/557C07D239/42C07D239/34C07D417/12C07D413/12C07D403/12C07D239/47C07D239/30C07D239/38C07D239/80C07D239/90C07D215/56C07D215/48C07D211/62A61P35/00
Inventor 张健陈颖毅黄敏黄志敏
Owner 上海宇道生物技术有限公司
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