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Selective phosphatidylinositol-3 kinase delta inhibitor

A compound, alkyl technology, used in the field of medicine

Inactive Publication Date: 2012-12-26
KBP BIOSCIENCES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, there are no PI3Kδ inhibitor drugs on the market. Therefore, it is necessary to develop more structural types of PI3Kδ inhibitors and select compounds with better efficacy and safety for the treatment of cancer and inflammation.

Method used

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  • Selective phosphatidylinositol-3 kinase delta inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0136] Example 1 Preparation of 2-(2-(9H-purin-6-yl)hydrazino)-5-fluoro-3-phenylquinazolin-4(3H)-one (compound 4)

[0137]

[0138] (1) Preparation of 2-fluoro-6-nitro-N-phenylbenzamide

[0139]

[0140] Dissolve 2-fluoro-6-nitrobenzoic acid (3.7 g, 20.0 mmol) in 40 mL CH 2 Cl 2 and 1.0mL DMF, slowly dropwise added oxalyl chloride (3.81g, 30.0mmol), stirred at room temperature for two hours, concentrated to remove the solvent, then dissolved in 4mL dioxane, and dropped it into aniline (1.86g ,20.0mmol), NaHCO 3 (3.36g, 40.0mmol) in dioxane (10mL) and water (10mL) solution, after the dropwise addition was completed, it was raised to room temperature and stirred for half an hour, then 200mL of water was added, a solid was precipitated, filtered by suction, and the solid was dried to obtain 5.13g of the product. Yield: 98.6%.

[0141] (2) Preparation of 2-amino-6-fluoro-N-phenylbenzamide

[0142]

[0143] Dissolve 2-fluoro-6-nitro-N-phenylbenzamide (5.2g, 20.0mmol) ...

Embodiment 2

[0164] Example 2 Preparation of 2-((9H-purin-6-yl)methylamino)-5-fluoro-3-phenylquinazolin-4(3H)-one (compound 5)

[0165]

[0166] (1) Preparation of 2-fluoro-6-nitro-N-phenylbenzamide

[0167]

[0168] Dissolve 2-fluoro-6-nitrobenzoic acid (3.7 g, 20.0 mmol) in 40 mL CH 2 Cl 2 and 1.0mL DMF, slowly dropwise added oxalyl chloride (3.81g, 30.0mmol), stirred at room temperature for two hours, concentrated to remove the solvent, then dissolved in 4mL dioxane, and dropped it into aniline (1.86g ,20.0mmol), NaHCO 3 (3.36g, 40.0mmol) in dioxane (10mL) and water (10mL) solution, after the dropwise addition was completed, it was raised to room temperature and stirred for half an hour, then 200mL of water was added, a solid was precipitated, filtered by suction, and the solid was dried to obtain 5.13g of the product. Yield: 98.6%.

[0169] (2) Preparation of 2-amino-6-fluoro-N-phenylbenzamide

[0170]

[0171] Dissolve 2-fluoro-6-nitro-N-phenylbenzamide (5.2g, 20.0mmol...

Embodiment 3

[0204] Example 3 Preparation of 2-((9H-purin-6-yl)methoxy)-5-fluoro-3-phenylquinazolin-4(3H)-one (compound 6)

[0205]

[0206] (1) Preparation of 6-chloro-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purine

[0207]

[0208] Under nitrogen protection, throw 6-chloro-9H-purine (20g, 129.40mmol) and N,N-dimethylformamide (200mL) into a 250mL four-neck round bottom flask, and hydrogenate in batches at -10°C Sodium (5.2g, 130.00mmol, content 60%), stirred for 30min. -10°C, (2-(chloromethoxy)ethyl)trimethylsilane (20.1g, 120.56mmol) was added dropwise while stirring within 20min, the resulting solution was stirred at 25°C overnight, and 1000mL of ice was added Quenched with water, extracted three times with 500 mL of ethyl acetate. The combined organic layers were washed three times with 50 mL of brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and subjected to silica gel column chromatography (ethyl acetate:petroleum ether=1:10) to obtain a yellow oil (22 g...

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Abstract

The invention belongs to the field of medical technology, and in particular relates to a selective phosphatidylinositol-3 kinase delta inhibitor shown in the formula (I), a salt of the selective phosphatidylinositol-3 kinase delta inhibitor, accepted in pharmacy, and a stereoisomer or a deuterated material of the selective phosphatidylinositol-3 kinase delta inhibitor, wherein X1, X2, X3, X4, Y, Z, W, R1 and R2 are defined as specification. The invention also relates to a preparation method of the compounds, medicinal preparations containing the compounds and application of the compounds in preparation of drugs for treating and / or preventing inflammatory diseases or tumors.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a selective phosphoinositide 3-kinase delta inhibitor, a pharmaceutically acceptable salt thereof, a stereoisomer or a deuterated product thereof, and a preparation method of these compounds, which contain these compounds pharmaceutical preparations, and the use of these compounds in the preparation of medicines for treating inflammatory diseases or tumors. Background technique [0002] Tumor is a new organism formed by the body under the action of various tumorigenic factors, causing changes in the genetic material of cells, resulting in abnormal gene expression and abnormal proliferation of cells. Tumor cells lose their normal growth regulation function and have the ability to grow independently or relatively independently. Even if the tumorigenic factors are stopped, tumor cells can continue to grow and consume a large amount of nutrients in the human body. If not...

Claims

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Application Information

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IPC IPC(8): C07D473/34C07D473/00A61K31/52A61P29/00A61P35/00
Inventor 吴永谦
Owner KBP BIOSCIENCES CO LTD
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