Novel pyrido[3,4-d]pyrimidin-8-one derivative having protein kinase inhibitory activity, and pharmaceutical composition for preventing, alleviating, or treating cancer, comprising same

A derivative, 4-d technology, applied in the direction of drug combination, organic active ingredients, medical preparations containing active ingredients, etc., can solve problems such as inability to establish treatment strategies and failure to achieve clinical therapeutic effects

Pending Publication Date: 2021-11-12
KOREA INST OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this also failed to achieve clinical therapeutic effect
In particular, in the case of STK33, demonstrated by cell-based pharmacological screens at the preclinical stage, a therapeutic strategy using KRAS mutations and synthetic lethal principles could not be established

Method used

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  • Novel pyrido[3,4-d]pyrimidin-8-one derivative having protein kinase inhibitory activity, and pharmaceutical composition for preventing, alleviating, or treating cancer, comprising same
  • Novel pyrido[3,4-d]pyrimidin-8-one derivative having protein kinase inhibitory activity, and pharmaceutical composition for preventing, alleviating, or treating cancer, comprising same
  • Novel pyrido[3,4-d]pyrimidin-8-one derivative having protein kinase inhibitory activity, and pharmaceutical composition for preventing, alleviating, or treating cancer, comprising same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0429] N-(3-(2-(cyclopropylamino)-7-methyl-8-oxo-7,8-dihydropyrido[3,4-d]pyrimidin-6-yl)-4-methyl phenyl)-3-(trifluoromethyl)benzamide

[0430]

[0431] Step 1: Methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate

[0432]

[0433]Acetyl chloride (1.1 equivalents, 10.5 mL) was dissolved in methanol (200 mL) at 0°C. After stirring at 0°C for 10 minutes, 5-bromo-2-(methylthio)pyrimidine-4-carboxylic acid (25 g, 1 equiv) was added slowly over 15 minutes. The reaction solution was refluxed for 4 hours and cooled. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The concentrate was diluted with dichloromethane, and then washed with saturated aqueous sodium bicarbonate, and then brine. The organic layer was dried over magnesium sulfate and concentrated. The concentrate was recrystallized from ethyl acetate and hexane, and then filtered to obtain the title compound (20 g, 76% yield) in yellow color.

[0434] 1 H-NMR: (400M...

Embodiment 2

[0482] N-(3-(2-((2-hydroxyethyl)amino)-7-methyl-8-oxo-7,8-dihydropyrido[3,4-d]pyrimidin-6-yl) -4-methylphenyl)-3-(trifluoromethyl)benzamide

[0483]

[0484] The experimental method is the same as that in Example 1, except that in step 12, 2-aminoethanol is used instead of cyclopropylamine. LCMS (ESI): 498 (M+H) + .

Embodiment 3

[0486] N-(4-methyl-3-(7-methyl-2-(methylamino)-8-oxo-7,8-dihydropyrido[3,4-d]pyrimidin-6-yl) Phenyl)-3-(trifluoromethyl)benzamide

[0487]

[0488] The experimental method is the same as that in Example 1, except that in step 12, methylamine is used instead of cyclopropylamine. LCMS (ESI): 468 (M+H) + .

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Abstract

The present invention relates to: a pyrido[3,4-d]pyrimidin-8-one derivative compound exhibiting excellent anti-proliferative effects on cancer cells, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a stereoisomer thereof; a preparation method therefor; a pharmaceutical composition for preventing, alleviating, or treating cancer metastasis and proliferative diseases, containing same as an active ingredient; and an anti-cancer composition used on cancer cells, wherein the compound exhibits excellent cancer cell inhibitory activities and anti-proliferative effects, thereby being useful in the inhibition of cancer cells and, further, in the prevention of cancer metastasis and proliferative diseases and in the cancer treatment.

Description

technical field [0001] The present disclosure relates to compounds selected from the group consisting of novel pyrido[3,4-d]pyrimidin-8-one derivatives having protein kinase inhibitory activity, pharmaceutically acceptable salts thereof, hydrates thereof, and stereoisomers thereof A body, a method for producing the compound, and a pharmaceutical composition comprising the compound for preventing, alleviating or treating cancer. Background technique [0002] Protein kinases are enzymes that catalyze the phosphorylation reaction that transfers the gamma-phosphate group from ATP to the hydroxyl groups of tyrosine, serine, and threonine on proteins. They are involved in cell metabolism, gene expression, cell growth, differentiation and cell division, and play an important role in cell signaling. [0003] Protein kinases make up about 2% of the eukaryotic genome, and there are about 518 protein kinases in the human genome. Protein kinases are classified into tyrosine protein ki...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/519A61P35/00
CPCA61P35/00C07D471/04C07D487/04A61K31/519
Inventor 沈台辅许祐荣宋致满桑迪普·森古普塔朴赞善崔丞惠赵汉娜慎忍宰
Owner KOREA INST OF SCI & TECH
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