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Biaryl amide structure containing sorafenib derivative as well as preparation method and applications thereof

A technology for arylamides and derivatives, applied in the field of sorafenib derivatives containing biarylamide structure and its preparation, can solve the problems of no inhibitory activity and weak effect

Inactive Publication Date: 2015-12-16
JIANGXI SCI & TECH NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Slightly weak on Ron, Flt-1 / 3 / 4, Kit, PDGFRα / β and Tie-2, little inhibitory activity on FGFR1 and EGFR

Method used

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  • Biaryl amide structure containing sorafenib derivative as well as preparation method and applications thereof
  • Biaryl amide structure containing sorafenib derivative as well as preparation method and applications thereof
  • Biaryl amide structure containing sorafenib derivative as well as preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] N-(4-(2-(Methylcarbamoyl)pyridin-4-yloxy)phenyl)-4-p-chlorophenylpyridinamide

[0099] Step a4-chloropicolinate chloride (formula 2)

[0100] Put 10g (0.081mol) of 2-pyridinecarboxylic acid, 1.3g (0.013mol) of sodium bromide and 13mL of chlorobenzene in a 250mL three-necked flask, after heating up to 50°C, slowly add 24mL of thionyl chloride dropwise, and the dropwise addition is complete Continue stirring for 3 minutes, heat up to 85°C, and reflux for 20 hours. After the reaction was completed, the solvent and excess thionyl chloride were evaporated under reduced pressure, and 15 mL of toluene was added and stirred for 5 minutes. After the solvent was evaporated, a yellow oily liquid was obtained, namely 4-chloropicolidinyl chloride, and 50 mL of toluene was added, and the solution was directly used react in the next step.

[0101] Step b4-chloro-N-picoline carboxamide (formula 3)

[0102] Put 30mL of 33% methylamine aqueous solution into a 250mL round-bottomed flas...

Embodiment 2

[0116] N-(4-(2-(Methylcarbamoyl)pyridin-4-yloxy)phenyl)-4-p-tolylpyridinamide

[0117] ESI-MS [M+Na] m / z: 461.1; 1 HNMR(400MHz,DMSO)δ10.92(s,1H),8.80(d,J=4.9Hz,2H),8.53(d,J=5.5Hz,1H),8.42(s,1H),8.10(d, J=8.7Hz, 2H), 8.01(s, 1H), 7.82(d, J=7.8Hz, 2H), 7.43(s, 1H), 7.40(d, J=7.6Hz, 2H), 7.27(d, J=8.6Hz, 2H), 7.20(s, 1H), 2.80(d, J=4.5Hz, 3H), 2.40(s, 3H).

Embodiment 3

[0119] N-(4-(2-(Methylcarbamoyl)pyridin-4-yloxy)phenyl)-4-phenylpyridineamide

[0120] ESI-MS [M+K] m / z: 463.2; 1 HNMR(400MHz,DMSO)δ10.91(s,1H),8.82(t,J=4.5Hz,1H),8.79(d,J=4.8Hz,1H),8.52(d,J=5.6Hz,1H) ,8.43(d,J=1.3Hz,1H),8.09(d,J=9.0Hz,2H),8.02(dd,J=5.1,1.8Hz,1H),7.94–7.88(m,2H),7.56( ddd,J=10.8,9.8,5.4Hz,3H),7.42(d,J=2.5Hz,1H),7.26(d,J=9.0Hz,2H),7.18(dd,J=5.6,2.6Hz,1H ),2.79(d,J=4.8Hz,3H).

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Abstract

The invention discloses a biaryl amide structure containing sorafenib derivative as well as a geometrical isomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a prodrug and a preparation method of the sorafenib derivative. The biaryl amide structure containing sorafenib derivative as well as the pharmaceutically acceptable salt, the hydrate or the solvate of the sorafenib derivative are taken as active components and mixed with a pharmaceutically acceptable carrier or excipient for preparation of composition and clinically acceptable dosage forms. The invention further discloses applications of the compound to preparation of drugs for treating and / or preventing hyperplastic diseases, preparation of drugs for treating and / or preventing cancer and preparation of drugs for treating and / or preventing prostate cancer and lung cancer.

Description

technical field [0001] The invention relates to sorafenib derivatives, in particular to a sorafenib derivative containing a biaryl amide structure and a preparation method and application thereof. Background technique [0002] Malignant tumor is a disease that seriously endangers human life and health. With the change of external factors such as environmental pollution, the number of cancer incidences in the world is increasing year by year. According to the statistics of the World Health Organization (WHO), about 10 million people are diagnosed every year in the world. Cancer patients, 7 million people died of related diseases caused by tumors, so malignant tumors have become the second major killer of human beings after cardiovascular diseases. [0003] Sorafenib (Sorafenib, BAY43-9006, trade name Nexevar) is a novel bisaryl urea small molecule oral multi-target receptor tyrosine kinase inhibitor developed by Bayer and Onyx Pharmaceuticals. In December 2005 and October 20...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/81C07D401/12A61K31/506A61K31/444A61P35/00
CPCC07D213/81C07D401/12
Inventor 郑鹏武朱五福武春江徐珊唐启东王文惠王敏陈乐张宇星
Owner JIANGXI SCI & TECH NORMAL UNIV