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Application of fluorine-substituted 2-aminothiazole-5-aromatic carboxamide

A technology of usage and metabolites, applied in the field of medicinal chemistry, can solve problems such as loss of activity, mutation of target protein, etc.

Inactive Publication Date: 2021-02-26
HUNAN WARRANT PHARMA +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But new genetic mutations and drug-resistant forms also emerge in clinical practice, necessitating further development of new inhibitors
Large doses of drugs can cause mutations in target proteins, leading to loss of activity

Method used

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  • Application of fluorine-substituted 2-aminothiazole-5-aromatic carboxamide
  • Application of fluorine-substituted 2-aminothiazole-5-aromatic carboxamide
  • Application of fluorine-substituted 2-aminothiazole-5-aromatic carboxamide

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0081] The synthesis of formula I compound:

[0082]

[0083] The synthetic route of formula I compound is as follows:

[0084] Synthesis of [5-(2-chloro-4-fluoro-6-methylphenylcarbamoyl)thiazol-2-yl]-carbamic acid tert-butyl ester

[0085]

[0086] N 2 Under gas protection, add 24.4g (0.1mol) of 2-tert-butoxycarbonylaminothiazole-5-carboxylic acid and 0.5ml of DMF (N,N-dimethylformamide) into 250ml of dichloromethane, and slowly add 13ml of Oxalyl chloride solution (0.15mol), reacted for 2h, and removed the solvent by rotary evaporation to obtain a white solid, which was dissolved in 100ml of anhydrous dichloromethane, and slowly added dropwise to 2-chloro-4-fluoro- In the methylene chloride solution of 17.5g (0.11mol) of 6-methylaniline (0.11mol) and N,N-diisopropylethylamine 38.8g (0.3mol), N 2 React at room temperature for 10 h under gas protection, distill off the solvent under reduced pressure, add a mixed solvent of 25 ml of ethyl acetate and 25 ml of n-hexane ...

Embodiment 1

[0097] The compound of formula I was used to study the activity of kinase inhibition in vitro and the metabolism of human liver microsomes.

[0098] 1. Kinase inhibitory activity study

[0099] 1.1 Experimental method

[0100] 1.1.1 Test drug preparation

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Abstract

The application of the invention relates to an application of a compound of a formula I or pharmaceutically acceptable salt, ester, solvate, prodrug, active metabolite, crystal, stereoisomer, tautomeror geometric isomer thereof, or a medical composition comprising the compound of the formula I or the pharmaceutically acceptable salt, the ester, the solvate, the prodrug, the active metabolite, thecrystal, the stereoisomer, the tautomer or the geometrical isomer to preparation of drugs for preventing or treating tyrosine kinase related diseases.

Description

technical field [0001] The application belongs to the field of medicinal chemistry, in particular to a fluorine-substituted 2-aminothiazole-5-aromatic carboxamide for the treatment and prevention of diseases and disorders or its pharmaceutical composition in diseases associated with tyrosine kinases (such as immune preventive or therapeutic use in diseases such as diseases, tumors and neurological diseases). Background technique [0002] Protein kinases are a class of enzymes that catalyze the phosphorylation of proteins, thereby altering their substrate activity or ability to bind to other proteins. Kinase signaling is the most common form of reversible post-translational modification and controls many aspects of cellular function. Aberrant activation of protein kinases is a major hallmark of malignancy, including alterations in cell proliferation, survival, motility, and metabolism, as well as disorders such as angiogenesis and evasion of antitumor immune responses. [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61K45/06A61P35/02A61P35/00A61P9/10A61P35/04A61P19/00A61P19/10A61P11/00A61P3/14A61P3/00A61P25/16A61P19/02A61P37/06A61P37/02A61P17/06A61P37/00A61P17/00A61P9/00A61P11/06A61P43/00
CPCA61K31/506A61K45/06A61P35/02A61P35/00A61P9/10A61P35/04A61P19/00A61P19/10A61P11/00A61P3/14A61P3/00A61P25/16A61P19/02A61P37/06A61P37/02A61P17/06A61P37/00A61P17/00A61P9/00A61P11/06A61P43/00A61P3/04
Inventor 皮士卿徐燕杨代鸿周志刚
Owner HUNAN WARRANT PHARMA
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