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4-Substituted-6-phenylpyrimidine derivatives containing ureido moieties and their preparation methods and uses

A technology of phenylpyrimidine and derivatives, applied in the field of medicinal chemical synthesis, can solve problems such as difficulty in meeting the needs of patients

Active Publication Date: 2016-06-01
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs that have been developed are still difficult to meet the needs of patients due to many factors.

Method used

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  • 4-Substituted-6-phenylpyrimidine derivatives containing ureido moieties and their preparation methods and uses
  • 4-Substituted-6-phenylpyrimidine derivatives containing ureido moieties and their preparation methods and uses
  • 4-Substituted-6-phenylpyrimidine derivatives containing ureido moieties and their preparation methods and uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] Example 12-((4-chloro-6-phenylpyrimidin-2-yl)thio)-N-(pyridyl-2-carbamoyl)acetamide

[0014] At 50°C, 6-phenyl-2-thiouracil (2.04g, 10.0mmol) was dissolved in 30ml of potassium hydroxide (0.4g, 10.0mmol) in aqueous solution, and then 2-chloro-N-(pyridine Base-2-carbamoyl) acetone solution (20ml) of acetamide (2.13g, 10.0mmol) was added dropwise to the reaction solution, continued to react for half an hour after the dropwise addition, filtered with suction, washed the filter cake with water and washed three times with acetone ( 3×10ml) to obtain pure 2-((4-hydroxy-6-phenylpyrimidin-2-yl)thio)-N-(pyridyl-2-carbamoyl)acetamide.

[0015] At 0°C, slowly add 10ml of thionyl chloride to the 2-((4-hydroxy-6-phenylpyrimidin-2-yl)thio)-N-(pyridyl-2-carbamoyl) synthesized above In acetamide (1.91g, 5.0mmol), after the addition, the temperature was slowly raised to 90°C, the reaction was continued for 1 hour, and then the reaction was stopped. After the reaction solution was coole...

Embodiment 2

[0017] Example 22-((4-((4-methylphenyl)amino)-6-phenylpyrimidin-2-yl)thio)-N-(pyridyl-2-carbamoyl)acetamide

[0018] The 2-((4-chloro-6-phenylpyrimidin-2-yl)sulfur)-N-(pyridyl-2-carbamoyl)acetamide (120.02mg, 0.3mmol) and p-methyl Aniline (38.57mg, 0.36mmol) was added to 5ml of glacial acetic acid, and then the temperature was raised to 90°C. After the reaction was detected by TLC, the reaction was stopped. Suction filtration while it was hot, and the filter cake was washed with glacial acetic acid (3×10ml).

[0019] White solid powder, yield 70.3%; 1 HNMR (400MHz, DMSO-d 6 ,δ,ppm):11.28(s,1H),10.77(s,1H),9.83(s,1H),8.28(d,J=4.8Hz,1H),8.00(dd,J=7.7,1.7Hz, 3H),7.83(t,J=7.8Hz,1H),7.66(d,J=8.0Hz,2H),7.48(dd,J=12.5,6.8Hz,3H),7.36(t,J=7.9Hz, 2H),7.16–7.10(m,1H),7.05(t,J=7.4Hz,1H),6.99(s,1H),4.20(s,2H). 13 CNMR (100MHz, DMSO-d 6 ,δ,ppm):171.70(s),169.56(s),161.58(s),161.20(s),151.17(s),150.89(s),148.30(s),139.87(s),139.36(s) ,136.81(s),131.01(s),129.29(d,J=2.4Hz),126.94(s),12...

Embodiment 3

[0020] Example 32-((4-((4-methoxyphenyl)amino)-6-phenylpyrimidin-2-yl)thio)-N-(pyridyl-2-carbamoyl)acetamide

[0021] In the method of Example 2, p-methylaniline is replaced with p-methoxyaniline and obtained.

[0022] White solid powder, yield 84.5%; 1 HNMR (400MHz, DMSO-d 6 ,δ,ppm):11.25(s,1H),10.77(s,1H),9.68(s,1H),8.28(d,J=4.5Hz,1H),7.98(t,J=7.3Hz,3H) ,7.83(t,J=7.8Hz,1H),7.52(d,J=8.6Hz,2H),7.47(t,J=6.3Hz,3H),7.16–7.10(m,1H),6.94(d, J=8.9Hz,2H),6.89(s,1H),4.18(s,2H),3.73(s,3H). 13 CNMR (100MHz, DMSO-d 6 ,δ,ppm):171.66(s),169.48(s),161.24(s),155.76(s),151.18(s),150.90(s),148.32(s),139.33(s),136.80(s) ,132.61(s),130.93(s),129.25(s),126.93(s),122.55(s),120.12(s),114.53(s),113.65(s),98.45(s),55.61(s) ,35.88(s).HR-MS(ESI) CalcdforC 25 h 22 N 6 o 3 S[M+H] + :487.1552,found:487.1551..

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Abstract

The invention belongs to the technical field of synthesis of pharmaceutical chemistry, and discloses 4-substituent-6-phenyl pyrimidine derivatives comprising carbamido fragments with antineoplastic activity and a preparation method, a synthetic method and use of the derivatives. A series of 4-substituent-6-phenyl pyrimidine derivatives comprising carbamido fragments are prepared through reactions such as cyclization, substitution, chlorination and ammonolysis on ethyl benzoylacetate as a raw material. The compounds provided by the invention have a structure shown as a formula I described in the specification, wherein X is N and CH, and R is Cl, 4-CH3-C6H5-NH2, 4-CH3O-C6H5-NH2. Antitumor activity in vitro experiment verifies that the compounds have remarkable inhibiting and killing effects to various tumor cells, and the compounds are further optimized to be expected to obtain novel anti-tumor drugs.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and relates to pyrimidine derivatives, in particular to 4-substituted-6-phenylpyrimidine derivatives containing ureido fragments with antitumor activity and their preparation methods and applications. Background technique [0002] Tumor is a disease that seriously endangers human health and is difficult to overcome. There are many anti-tumor drugs that have been marketed. Pyrimidine compounds have a wide range of biological activities, such as anti-virus, anti-bacterial, anti-inflammatory and anti-tumor. However, these drugs that have been developed are still difficult to meet the needs of patients due to many factors. Therefore, the research and development of new anticancer drugs is particularly important. There are few reports on the combination of pyrimidine and urea compounds. Therefore, the 4-substituted-6-phenylpyrimidine derivatives containing ureido moieties of the prese...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/12C07D239/38C07D239/47A61P35/00
CPCC07D239/38C07D239/47C07D401/12
Inventor 刘宏民张秋荣邵坤鹏章旭耀张孝松顾一飞陈鹏举薛登启贺鹏
Owner ZHENGZHOU UNIV