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2,7-naphthyridine derivative, and preparation method and application thereof

The technology of a compound, R22, is applied in 2 fields

Active Publication Date: 2013-03-20
HAINAN SIMCERE PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, 2,7-naphthyridine-1 (2H)-ketones have not been reported for the treatment of tyrosine kinase and / or serine-threonine kinase inhibitors

Method used

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  • 2,7-naphthyridine derivative, and preparation method and application thereof
  • 2,7-naphthyridine derivative, and preparation method and application thereof
  • 2,7-naphthyridine derivative, and preparation method and application thereof

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preparation example Construction

[0103] The present invention also relates to a preparation method with general formula (I), characterized in that it comprises,

[0104] a. Base segment (V) and chlorinated heterocycle (VI) in solvent S 1 Alkaline B 1 , Catalyst C 1 , Ligand L 1 In the presence of temperature T 1 Under the conditions, the reaction produces compound (I).

[0105]

[0106] or

[0107] b. Base fragment (V) and chlorinated heterocycle (VI) in solvent S 2 Medium acid A 1 In the presence of temperature T 2 Under the conditions, the reaction produces compound (I).

[0108]

[0109] where A, B, X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and m as above.

[0110] In order to prepare the compound described in the general formula (I) of the present invention, the preparation method is characterized in that, in the preparation process, the solvent S 1 Be selected from ether solvents, such as 1,4-dioxane, ethylene glycol dimethyl ether, preferably 1,4-dioxane; the base B 1 Selected from in...

specific Embodiment approach

[0128] The invention discloses a compound and its preparation method, an intermediate of the compound and its preparation method, and the application of the compound as a tyrosine kinase and / or serine-threonine kinase inhibitor. Those skilled in the art can Learn from the content of this article, and appropriately improve the process parameters to achieve. In particular, it should be pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and the relevant personnel can obviously make changes or appropriate changes and combinations to the method and application described herein without departing from the content, spirit and scope of the present invention to realize and Apply the technology of the present invention.

[0129] Below in conjunction with embodiment, fu...

Embodiment 1

[0130] Embodiment 1: the preparation of compound 1

[0131]

[0132] 2-Benzyl-8-((4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluorophenyl)amino)-2,7-naphthyridine-1 (2H)-Kone

[0133] Add 4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluoroaniline (50 mg, 1.0 eq), 2-benzyl-8-chloro-2 , 7-naphthyridin-1(2H)-one (42.9mg, 1.0eq), tris(dibenzylideneacetone)dipalladium (29.2mg, 0.2eq), 1,2-bis(diphenylphosphino)propane (26mg, 0.4eq), sodium tert-butoxide (19.8mg, 1.3eq) and 1,4-dioxane (10mL), pump nitrogen three times, react at 106°C for 4 hours, spot reaction is complete, cool to Room temperature, suction filtration, concentration, crude silica gel column chromatography (PE / EA 6 / 1 to 3.5 / 1) to obtain 2-benzyl-8-((4-((6,7-dimethoxyquinazoline- 4-yl)oxy)-3-fluorophenyl)amino)-2,7-naphthyridin-1(2H)-one (10.8mg), MS: [M+H] + =550.1.

[0134] 1 H-NMR (500M, DMSO-d 6 )δ12.11(b, 1H), 8.57(s, 1H), 8.29-8.30(d, 1H), 8.24-8.27(d, 1H), 7.87-7.89(d, 1H), 7.59(s, 1H) , 7.48-7.50(d, 1H), 7....

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Abstract

The invention discloses a 2,7-naphthyridine derivative and a preparation method and application thereof. The derivative is a compound with a structure represented by the formula I, or a pharmaceutically acceptable equivalent or salt thereof. The compound represented by the formula has a good inhibiting effect against various kinase activities. Half inhibitory concentrations of the compound against kinases such as c-Met, KDR, c-kit, and the like are generally lower than 10<-7>mol.L<-1>. Also, according to the embodiment of the invention, the compound with the structure of the formula I has an inhibiting effect against the proliferation of various tumor cells. The formula I is represented as the following.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to a class of 2,7-naphthyridine derivatives. The present invention also relates to a preparation method of such compounds and their use as tyrosine kinase inhibitors or serine-threonine kinase inhibitors. application. Background technique [0002] Mammalian cells share similar molecular mechanisms that regulate cell proliferation, differentiation and death throughout the cell cycle. Among them, protein tyrosine kinase and protein serine / threonine kinase play an important role in the signal transduction mechanism of normal cells, and their abnormal expression will lead to the generation of many diseases, such as tumor, arteriosclerosis, psoriasis and inflammatory response, etc. , thus regulating the activity of these kinases and restoring physiological balance can be used as a new treatment. [0003] The tyrosine kinase family is widely involved in cellular signal transduction as...

Claims

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Application Information

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IPC IPC(8): C07D519/00C07D471/04A61K31/519A61K31/444A61K31/517A61K31/5377A61K31/4375A61K31/4545A61K31/4985A61K31/4709A61P35/00
Inventor 黄伟丛欣明志会叶军赵兴俄王佳袁云霞
Owner HAINAN SIMCERE PHARMA CO LTD
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