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2-phenyl quinazoline derivative, preparation method thereof, and application in preparation of anti-cancer drugs

A technology of phenylquinazoline and derivatives, which is applied in the directions of antitumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problem that the binding stability of G-quadruplex needs to be improved, and achieve good binding ability and selection ability, Significant inhibitory effect, the effect of broad market prospects

Inactive Publication Date: 2013-04-03
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the quinazoline derivatives have effectively improved the compound's ability to select G-quadruplexes, the ability to bind and stabilize G-quadruplexes still needs to be improved

Method used

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  • 2-phenyl quinazoline derivative, preparation method thereof, and application in preparation of anti-cancer drugs
  • 2-phenyl quinazoline derivative, preparation method thereof, and application in preparation of anti-cancer drugs
  • 2-phenyl quinazoline derivative, preparation method thereof, and application in preparation of anti-cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035]Example 1: Synthesis of compound QH-2

[0036] 100mmol of 2-nitrobenzoic acid was dissolved in 50ml of thionyl chloride, refluxed for 1.5h, and then the thionyl chloride was evaporated, and the obtained brown liquid was slowly added dropwise to 125mmol of anthranilamide and 250 mmol triethylamine in chloroform (250 ml) solution, stirred at room temperature for 6 h, filtered, washed with ethanol, and recrystallized with ethanol to obtain a white solid QH-2.

[0037] Yield: 88%; 1 H NMR(400MHz, DMSO)δ12.57(s,1H),8.53(d,J=8.2Hz,1H),8.43(s,1H),8.13(d,J=8.3Hz,1H),7.95–7.78 (m,5H),7.62(dd,J=11.4,4.0Hz,1H),7.29-7.22(m,1H).LC-MS m / z:286[M+H] + .

[0038]

[0039] Compound QH-2

Embodiment 2

[0040] Example 2: Synthesis of compound QC-2

[0041] The method is the same as in Example 1, except that 4-chloro-2-nitrobenzoic acid is used instead of 2-nitrobenzoic acid to obtain white solid QC-2.

[0042] Yield: 80%; 1 H NMR (400MHz, DMSO-d 6 )δ12.56(s,1H),8.44(d,J=8.2Hz,1H),8.39(s,1H),8.26(d,J=1.6Hz,1H),8.04–7.96(m,1H), 7.93–7.85(m, 2H), 7.81(s, 1H), 7.59(t, J=7.8Hz, 1H), 7.24(t, J=7.6Hz, 1H). LC-MS m / z: 320[M +H] + .

[0043]

[0044] Compound QC-2

Embodiment 3

[0045] Example 3: Synthesis of compound QH-3

[0046] After mixing 88 mmol of dry QH-2 with 100 ml of 10% potassium hydroxide aqueous solution and 100 ml of ethanol, react at 95°C for 3 to 4 hours. After the reaction was completed, ethanol was distilled off, and the pH value of the solution was adjusted to between 1 and 3 with hydrochloric acid, a large amount of white solids were precipitated, filtered and dried, and petroleum ether / ethyl acetate (volume ratio 3 / 1) was used as the eluent to pass through. Purification by silica gel chromatography gave QH-3 as a white solid.

[0047] Yield: 98%; 1 H NMR(400MHz, DMSO)δ12.86(s,1H),8.27-8.16(m,2H),7.95-7.81(m,4H),7.67(d,J=7.8Hz,1H),7.62-7.56( m,1H).LC-MS m / z:268[M+H] + .

[0048]

[0049] Compound QH-3

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Abstract

The invention relates to the field of medicinal chemistry, in particular to a 2-phenyl quinazoline derivative. The 2-phenyl quinazoline derivative has the structural formula in the figure, wherein R1 is NH(CH2)3N(CH3)2; R2 is C1 or H; R3 is NHCO(CH2)nNR4 or NHCO(CH2)nNH(CH2)nNR4; n is equal to 1, 2, 3, 4 or 5; NR4 represents two C1-6 alkyls on an N atom, two C3-6 naphthenic bases or NR4 represents morpholinyl, piperazinyl or pyrrolidinyl. The invention further discloses a preparation of the 2-phenyl quinazoline derivative. The 2-phenyl quinazoline derivative has strong inhibition to telomere DNA expression, can significantly inhibit multiple kinds of cancer cell lines, has small toxicity to normal cells, and can be widely applied to preparation of anti-cancer drugs.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, and more particularly, to a 2-phenylquinazoline derivative, a preparation method thereof, and an application in the preparation of anticancer drugs. Background technique [0002] Cancer is one of the major diseases that threaten human health and life. According to statistics, there are about 4 million new cancer patients in the world every year. The research and development of anticancer drugs has always been the focus of attention of chemists and pharmacologists. It is one of the important directions of drug research and development to find anticancer drugs with high efficiency, high selectivity and less toxic and side effects. Designing and synthesizing anticancer drugs using DNA as a target, especially designing and synthesizing small molecule inhibitors for the special high-level structures of telomere DNA and c-myc and other proto-oncogene DNA with important physiological significance, i...

Claims

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Application Information

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IPC IPC(8): C07D239/94A61K31/517A61K31/5377A61P35/00A61P35/02
Inventor 黄志纾古练权何锦辉李增谭嘉恒欧田苗刘慧云
Owner SUN YAT SEN UNIV
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