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Pyrimidothiophene derivatives, and preparation method and application thereof in medicines

A kind of technology of compound, general formula, is applied in the field as MCL-1 inhibitor

Active Publication Date: 2020-04-07
JIANGSU HENGRUI MEDICINE CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Novartis, Amgen and AstraZeneca have all developed small molecule inhibitors against MCL-1, but they are still in the clinical stage, so further development of MCL-1 inhibitor drugs is needed

Method used

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  • Pyrimidothiophene derivatives, and preparation method and application thereof in medicines
  • Pyrimidothiophene derivatives, and preparation method and application thereof in medicines
  • Pyrimidothiophene derivatives, and preparation method and application thereof in medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0204] (R)-2-(((S)-6-(bicyclo[4.2.0]oct-1(6),2,4-trien-3-yl)-5-(3-chloro-2- Methyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)thieno[2,3-d]pyrimidin-4-yl)oxy)-3-(2 -((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoic acid 1

[0205]

[0206]

[0207] first step

[0208] 2-(bicyclo[4.2.0]oct-1(6),2,4-trien-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaboron Heterocyclopentane 1c

[0209] 4-4-Bromo-1,2-dihydrocyclobutylbenzene 1a (1.00g, 5.46mmol, purchased from Pide), biboronic acid pinacol ester 1b (1.67g, 6.58mmol), [1,1' -bis(diphenylphosphino)ferrocene]palladium dichloride (400mg, 0.55mmol), 1,1'-bis(diphenylphosphino)ferrocene (400mg, 0.55mmol) and potassium acetate (1.61 g, 16.41 mmol) was dissolved in 20 mL of dioxane, replaced with argon three times, and the reaction solution was heated to 90° C. under an argon atmosphere and stirred for 16 hours. The reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, ...

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PUM

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Abstract

The invention relates to pyrimidothiophene derivatives, and a preparation method and an application thereof in medicines. Specifically, the invention relates to the pyrimidothiophene derivatives represented by a general formula (I) and the preparation method thereof, a pharmaceutical composition containing the derivatives and the application of the pyrimidothiophene derivatives as therapeutic agents, especially as MCL-1 inhibitors, wherein substituent groups of the general formula (I) are the same as definitions in the specification.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a pyrimidothiophene derivative represented by general formula (I), its preparation method, a pharmaceutical composition containing the derivative and its use as a therapeutic agent, especially as an MCL-1 inhibitor the use of. Background technique [0002] An important feature that distinguishes tumor cells from normal cells is that apoptosis is inhibited, which gives them a greater survival advantage. Apoptosis, also known as programmed death, can be divided into exogenous apoptosis and endogenous apoptosis. Among them, endogenous apoptosis is an important barrier for the occurrence and development of cancer. BCL-2 family proteins are important regulators of endogenous apoptosis [0003] BCL-2 family proteins mainly exist on the mitochondrial membrane, and can be divided into two categories: anti-apoptotic proteins and pro-apoptotic proteins according to their functions. Anti-apoptotic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04A61P35/00A61P35/02A61K31/519A61K31/5377
CPCC07D495/04A61P35/00A61P35/02
Inventor 张国宝胡伟民贺峰陶维康
Owner JIANGSU HENGRUI MEDICINE CO LTD