Use of pteridinone derivatives as FLT3 inhibitors

A compound, C1-C3 technology, applied in the field of treatment of FLT3-mediated diseases, can solve the problems of no practical application value and unsatisfactory clinical effect.

Active Publication Date: 2017-03-01
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, no FLT3 inhibitor has been approved for clinical use, and the clinical effects of many FLT3 inhibitors in clinical trials are still not ideal
Many FLT3 inhibitors in the prior art inhibit the IC of FLT3 50 The value reaches hundreds or even thousands of nm, which has no practical application value

Method used

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  • Use of pteridinone derivatives as FLT3 inhibitors
  • Use of pteridinone derivatives as FLT3 inhibitors
  • Use of pteridinone derivatives as FLT3 inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0113] The concrete synthetic method of above-mentioned steps a-f is as follows:

[0114] Synthesis of tert-butyl (4-(2-chloro-5-nitropyrimidine-4-amino)phenyl)carbamate (step a)

[0115]

[0116] Weigh 2,4-dichloro-5-nitropyrimidine (190mg, 0.98mmol), add 6mL 1,4-dioxane, place in a 25mL round bottom flask, stir at room temperature, take (4-aminobenzene Base) tert-butyl carbamate (200mg, 0.96mmol), N,N-diisopropylethylamine (137mg, 1.06mmol) were dissolved in 4mL 1,4-dioxane, and slowly added dropwise to the above reaction solution After the dropwise addition, the mixture was stirred at room temperature for about 1 hour, and the reaction was completely converted as monitored by TLC. The solvent was removed by rotary evaporation, and the crude product was separated by silica gel column chromatography (petroleum ether / ethyl acetate=10:1, v / v) to obtain (4-(2-chloro-5-nitropyrimidine-4-amino)phenyl ) tert-butyl carbamate orange solid 301 mg, yield 82%. 1 H NMR (400MHz, DMS...

Embodiment 2

[0179] Biological Activity Test Section

[0180] The in vitro inhibitory effect experiment of the compounds provided by the invention on FLT3 kinase activity was carried out as follows, wherein FLT3 was purchased from BPS, MLN518 and AC220 were used as reference compounds, and the reference compounds were purchased from Selleck. The two structures were as follows:

[0181]

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PUM

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Abstract

The invention relates to pteridinone derivatives as FLT3 inhibitors and a use thereof. The invention relates to a compound shown in the formula I, a pharmaceutical composition containing the compound shown in the formula I and a use of the compound in preparation of drugs for treating FLT3-mediated diseases or inhibiting FLT3.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry; Specifically, the present invention relates to novel pteridinone derivatives, its synthesis method and its role as FMS-like tyrosine kinase 3 (FMS-like tyrosine kinase 3, FLT3) inhibitor in the treatment of FLT3 mediated diseases such as tumor applications. Background technique [0002] Protein tyrosine kinase (protein tyrosine kinase) is a class of proteins that catalyze the transfer of γ-phosphate on ATP to specific amino acid residues in proteins. It plays a very important role in intracellular signal transduction pathways and regulates cell growth, A series of physiological processes such as differentiation and death. It has been shown that more than 50% of proto-oncogenes and their products have protein tyrosine kinase activity, and their abnormal expression will lead to the disorder of cell life cycle, and then lead to the occurrence of tumors. In addition, abnormal expression o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D475/00A61K31/519A61P35/00A61P35/02A61P37/02A61P19/02A61P19/04A61P29/00A61P1/00A61P3/10A61P21/04A61P17/06A61P37/06A61P25/00A61P37/08A61P11/02
CPCC07D475/00
Inventor 李洪林徐玉芳陈卓赵振江吕剑昆孙德恒杨宇周伟
Owner EAST CHINA UNIV OF SCI & TECH
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