Benzopyrimidine-containing SYK inhibitor

A monocyclic and cycloalkyl technology, applied in medical preparations containing active ingredients, anti-inflammatory agents, organic chemistry, etc., can solve problems such as high price, difficult promotion, and large side effects

Inactive Publication Date: 2014-03-26
KBP BIOSCIENCES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing therapeutic drugs mainly include non-steroidal anti-inflammatory drugs and steroids, but these drugs have large side effects and cannot meet the long-term clinical needs
In addition, the latest progress in rheumatoid drugs is the application of some biological agents, such as TNF-α inhibitors and IL-1β antagonists. Although patients are well tolerated, their prices are high and it is difficult to widely promote them.

Method used

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  • Benzopyrimidine-containing SYK inhibitor
  • Benzopyrimidine-containing SYK inhibitor
  • Benzopyrimidine-containing SYK inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Example 1 4-[3-(2H-1,2,3-triazol-2-yl)anilino]-2-((cis)-2-aminocyclohexylamino)pyrido[4, 3-d] Preparation of pyrimidin-5(6H)-one (compound 4)

[0180] (1) ethyl 4-[3-(2H-1,2,3-triazol-2-yl)anilino]-6-methyl-2-(methylmercapto)pyrimidine-5-carboxylate

[0181]

[0182] Ethyl 4-chloro-6-methyl-2-(methylmercapto)pyrimidine-5-carboxylate (2.5g, 10.13mmol), 3-(2H-1,2,3-triazol-2-yl ) aniline (1.78g, 11.14mmol), and sodium acetate trihydrate (3.03g, 22.3mmol) were dissolved in 40mL of ethanol, heated at 80°C for overnight reaction, the solvent was evaporated to dryness, and the residue was dissolved in ethyl acetate, washed with water, and dried After concentration, it was separated by silica gel column (dichloromethane:methanol=100:1) to obtain 2.25g of product, the yield was 60%.

[0183] (2) 4-[3-(2H-1,2,3-triazol-2-yl)anilino]-6-methyl-2-(methylmercapto)pyrimidine-5-carboxylic acid

[0184]

[0185] Ethyl 4-[3-(2H-1,2,3-triazol-2-yl)anilino]-6-methyl-2-(methylmer...

Embodiment 2

[0200] Example 2 (S)-2-[4-[3-(2H-1,2,3-triazol-2-yl)anilino]pyrido[4,3-d]pyrimidine-5(6H) Preparation of -keto-2-ylamino]butyramide (Compound 1)

[0201]

[0202] Operation is the same as in Example 1 (6), and the productive rate is 9.7%.

[0203] Mass Spectrum (m / e): 405.9 (M+1)

[0204] 1 H-NMR (400MHz, d 6 -DMSO, δ ppm ):0.94(m, 3H), 1.85(m, 2H), 4.43(m, 1H), 6.13(m, 1H), 7.05(s, 1H), 7.18(m, 1H), 7.4(m, 2H) , 7.54(m, 1H), 7.75(m, 1H), 7.84~8.06(m, 1H), 8.14(m, 2H), 8.14~8.54(m, 1H), 11.4(m, 1H), 12.2(m , 1H).

Embodiment 3

[0205] Example 3 (S)-2-[4-[3-(2H-1,2,3-triazol-2-yl)anilino]pyrido[4,3-d]pyrimidine-5(6H) Preparation of -keto-2-ylamino]-4-methylpentanamide (compound 2)

[0206]

[0207] Operation is the same as in Example 1 (6), and the productive rate is 5.2%.

[0208] Mass Spectrum (m / e): 434.3 (M+1)

[0209] 1 H-NMR (400MHz, CD 3 OD, δ ppm ):0.88~1.0(m, 6H), 1.29(m, 1H), 1.32(m, 1H), 2.12(m, 1H), 4.60(m, 1H), 6.3(m, 1H), 7.37(m, 1H), 7.51(m, 2H), 7.81(s, 1H), 7.99(m, 2H), 9.04(m, 1H).

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PUM

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Abstract

The invention belongs to the technical field of medicine, and particularly relates to a benzopyrimidine-containing SYK inhibitor show in general formula (I) and pharmaceutically acceptable salt, stereoisomeride or solvate thereof, wherein X, Y, R1, R2, R3 and R4 are as defined in the specification. The invention also relates to a preparation method of these compounds, a pharmaceutical preparation containing these compounds and application of these compounds in preparation of medicaments for treating and / or preventing diseases related to syk-mediated signal paths.

Description

technical field [0001] The present invention belongs to the technical field of medicine, and specifically relates to a SYK inhibitor containing a pyrimido ring, its pharmaceutically acceptable salt, its stereoisomer or its solvate, a preparation method of these compounds and a pharmaceutical preparation containing these compounds, and Use of these compounds, their pharmaceutically acceptable salts, their stereoisomers or their solvates in the preparation of medicines for treating and / or preventing diseases related to syk-mediated signaling pathways. Background technique [0002] Protein tyrosine kinases (PTKs) are a group of proteases that can catalyze the phosphorylation of substrate protein tyrosine residues, participate in many signal transduction pathways, and play an important role in the control of cell differentiation, proliferation and spread . According to the different cellular topology of PTKs family members, they can be divided into receptor type and non-recepto...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/519A61P29/00A61P35/00A61P11/06A61P37/08A61P19/02A61P27/02A61P35/02A61P17/06A61P37/02
CPCC07D471/04
Inventor 罗浩贤王爱臣
Owner KBP BIOSCIENCES CO LTD
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