Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

2-aminothiazole-4-amide derivative, its preparation method and application

A reaction and group technology, which is applied in the field of 2-aminothiazole-4-amide derivatives and their preparation, can solve the problems of side effects and drug resistance, and achieve simple reactions, correct structures, and easy-to-obtain raw materials Effect

Active Publication Date: 2015-04-08
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Tumor is a common and frequently-occurring disease. Cancer has seriously threatened human health and life. The combination of traditional surgery, chemotherapy and radiotherapy has successfully improved the cure rate of malignant tumors, but it will bring side effects and drug resistance.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 2-aminothiazole-4-amide derivative, its preparation method and application
  • 2-aminothiazole-4-amide derivative, its preparation method and application
  • 2-aminothiazole-4-amide derivative, its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0036] Example 1: Preparation of compound N-(2-chloropyridin-5-yl)-2-(2-benzamidothiazol-4-yl)acetamide (R in formula I 1 = H, R 2 =-COCl,R 3 = N, R 4 = S, R 5 = N, R 6 = Cl, R 7 =H, the compound of n=0)

[0037] Step 1): Add 3.9 g (0.02 mol) of ethyl 2-aminothiazole-4-acetate in a 100 ml three-necked flask, add 50 ml of tetrahydrofuran, and add 3.32 ml (0.02 mol) of benzoyl chloride dropwise in an ice bath, Reaction at room temperature for 8 hours, then poured into 100ml of water, with saturated NaHCO 3 Wash with aqueous solution, extract 30ml×3 with dichloromethane, wash with 2M dilute HCl solution, dry over anhydrous sodium sulfate, and concentrate to obtain the product ethyl 2-benzamidothiazole-4-acetate.

[0038]Step 2): put the compound 2-benzoylaminothiazole-4-ethyl acetate obtained in step 1 into a 250ml round bottom flask, add ethanol-water-sodium hydroxide (7:3, v / v; 1.5mol / L) 50ml, refluxed for 0.5 hours, cooled to room temperature, adjusted to pH 4-5, whit...

example 2

[0043] Example 2: Preparation of N-(2-chloropyridin-5-yl)-2-[3-(3,4dichlorophenyl)ureido]thiazole-4-carboxamide (R in formula I 1 =3,4-dichloro, R 2 =-NCO,R 3 =N,R 4 =S, R 5 =N,R 6 =Cl, R 7 =H, compounds with n=0)

[0044] Step 1): add 2-aminothiazole-4-ethyl carboxylate 3.5g (0.02mol) in a 100ml three-necked flask, add 50ml tetrahydrofuran, add 3.7g (0.02mol) of 3,4-dichlorobenzene isocyanate, The reaction was carried out at room temperature for 12 hours, and then poured into 100 ml of water and saturated with NaHCO. 3 Washed with aqueous solution, extracted with dichloromethane 30ml×3, washed with 2M dilute HCl solution, dried over anhydrous sodium sulfate, and concentrated to obtain the product 2-[3-(3,4dichlorophenyl)ureido]thiazole- 4-ethyl formate.

[0045] Step 2): put the compound 2-[3-(3,4dichlorophenyl)ureido]thiazole-4-carboxylic acid ethyl ester obtained in step 1 into a 250ml round bottom flask, add ethanol-water-sodium hydroxide (7:3, v / v; 1.5mol / L) 50ml...

example 3

[0050] Example 3: Preparation of N-(2-hydroxy-1-methoxycarbonylphen-5-yl)-2-[3-(3,4dichlorophenyl)ureido]thiazole-4-carboxamide (Formula I Medium R 1 =3,4-dichloro, R 2 =-NCO,R 3 =N,R 4 =S, R 5 =C,R 6 =OH, R 7 =-COOCH 3 , compounds with n=0)

[0051] Step 1): add 3.9g (0.02mol) of 2-aminothiazole-4-ethyl acetate into a 100ml three-necked flask, add 50ml tetrahydrofuran, add 3.7g (0.02mol) of 3,4 dichlorobenzene isocyanate, room temperature The reaction was continued for 12 hours, then poured into 100 ml of water with saturated NaHCO 3 Washed with aqueous solution, extracted with dichloromethane 30ml×3, washed with 2M dilute HCl solution, dried over anhydrous sodium sulfate, and concentrated to obtain the product 2-[3-(3,4dichlorophenyl)ureido]thiazole- 4-ethyl acetate.

[0052] Step 2): put the compound 2-[3-(3,4dichlorophenyl)ureido]thiazole-4-ethyl acetate obtained in step 1 into a 250ml round bottom flask, add ethanol-water-sodium hydroxide (7:3, 1.5mol / L) 50ml, ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a 2-aminothiazole-amide derivative, its preparation method and application. The structural formula of the compound is shown as formula I, wherein R1 is H, or one or more of the following mono-substituted or multi-substituted groups on a benzene ring: fluorine, chlorine, bromine, methyl, methoxyl, hydroxyl, nitro, amino, trifluoromethyl and cyano; R2 is -CH2-, -CO-, -NHCO- or -S02-; R3 is C or N; R4 is C, N, O or S; R5 is C or N; R6 is hydrogen, fluorine, chlorine, bromine, methyl, methoxyl, hydroxyl, mercapto, amino, methylamino, ethylamino, morpholine, piperazine, methyl piperazine, ethyl piperazine, benzyl piperazine, p-methoxyl benzyl piperazine or p-chlorobenzyl piperazine; R7 is -H, -F, -Cl, -Br, -COOCH3, -COOCH2CH3, -CONH2, -CONHCH3 or -CONHCH2CH3; and n is 0 or 1 or 2. The compound provided in the invention has very good anti-tumor activity, and has important practical value and application prospects in the antitumor medicine preparation field. (Formula I).

Description

technical field [0001] The invention relates to a 2-aminothiazole-4-amide derivative and its preparation method and application. Background technique [0002] Tumor is a common and frequently-occurring disease. Cancer has seriously threatened human health and life. The combination of traditional surgery, chemotherapy and radiotherapy has successfully improved the cure rate of malignant tumors, but it will bring side effects and drug resistance. . Now, with the continuous deepening of the research on cell signal transduction pathways, people have a deeper understanding of the role of oncogenes and anti-cancer genes inside tumor cells, making it possible to design new tumor-specific molecular targets with less side effects. , Anticancer drugs with low drug resistance become possible. [0003] Protein tyrosine kinases (PTKs) are extremely important substances in the process of cell signal transduction, and its overexpression will activate its downstream signaling pathways, le...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D277/38C07D277/56C07D417/12A61K31/426A61K31/4439A61P35/00
Inventor 蒋宇扬丁怀伟张存龙谭春燕
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com