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Anilinoquinazoline compound containing nitroimidazole group and preparation method and application thereof

A compound and nitro technology, applied in the field of aniline quinazoline compounds and their preparation, can solve the problems of insignificant curative effect, lack of similar compounds and the like

Active Publication Date: 2017-04-19
INST OF RADIATION MEDICINE CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The present invention aims at the technical defects of the prior art, and provides a kind of aniline quinazoline compound containing nitroimidazole group and its preparation method and application, so as to solve the technical problem of lacking a similar compound in the prior art
[0007] Another technical problem to be solved by the present invention is that the curative effect of drugs used to inhibit the EGFR signaling pathway in the prior art is not obvious

Method used

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  • Anilinoquinazoline compound containing nitroimidazole group and preparation method and application thereof
  • Anilinoquinazoline compound containing nitroimidazole group and preparation method and application thereof
  • Anilinoquinazoline compound containing nitroimidazole group and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 14

[0060] Example 1 Preparation of 4-hydroxymethylpiperidine-1-carboxylate tert-butyl ester

[0061] Synthesized with reference to the literature J.Med.Chem., 2002, 45, 1300. White solid; melting point 74.3-76.1°C; yield 93.8%. MS M / z: 214.77 [M-1]; 1 H NMR (400MHz, DMSO-d 6 )δ0.95(ddd, J 1 =24.8Hz, J 2 =12.8Hz, J 3 =4.4Hz, 2H), 1.37(s, 9H), 1.49(m, 1H), 1.59(d, J=13.2Hz, 2H), 2.65(s, 2H), 3.23(t, J=6.0Hz, 2H) ), 3.93 (d, J=12.4 Hz, 2H), 4.42 (t, J=5.2 Hz, 1H).

Embodiment 24

[0062] Example 2 Preparation of 4-methylbenzenesulfonic acid-(1-tert-butoxycarbonylpiperidin-4-yl)methyl ester

[0063] Synthesized with reference to the literature J.Med.Chem., 2002, 45, 1300. White solid; melting point 72.4-73.6°C; yield 85.2%. MS M / z: 370.18[M+1]; 1 H NMR (400MHz, DMSO-d 6 )δ0.96(ddd, J 1 =24.4Hz, J 2 =12.4Hz, J 3 =4.4Hz, 2H), 1.36(s, 9H), 1.53(d, J=11.2Hz, 2H), 1.76(m, 1H), 2.41(s, 3H), 2.63(s, 2H), 3.87(d , 4H), 7.47(d, J=8.0Hz, 2H), 7.77(d, J=8.0Hz, 2H).

Embodiment 34

[0064] Example 3 Preparation of 4-p-toluenesulfonyloxymethylpiperidine methanesulfonate

[0065] Synthesized with reference to J.Org.Chem.2010, 75, 8117. White solid; melting point 113.0-114.5°C; yield 84.3%. MS M / z: 270.38[M+1]; 1 H NMR (400MHz, DMSO-d 6)δ1.31(m, 2H), 1.72(d, J=12.8Hz, 2H), 1.93(m, 1H), 2, 32(s, 3H), 2.42(s, 3H), 2.83(m, 2H) ), 3.23(d, J=12.8Hz, 2H), 3.92(d, J=6.0Hz, 2H), 7.48(d, J=8.4Hz, 2H), 7.78(d, J=8.4Hz, 2H), 8.12(br s, 1H), 8.50(br s, 1H).

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Abstract

The invention provides a brand new anilinoquinazoline compound of the structure in the formula (I). The anilinoquinazoline compound has a tyrosine kinase inhibiting effect. Real-time fluorogenic quantitative PCR measurement results indicate that the VEGF expression quantity is reduced by 1000 times or more through the target compound, the inhibiting effect on VEGF expression is quite obvious, and the inhibiting activity is far higher than that of vandetanib. Further experiments indicate that the target compound has the better antineoplastic activity compared with vandetanib under the anoxia condition and is expected to be the medicine for treating tumors.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a nitroimidazole group-containing aniline quinazoline compound and a preparation method and application thereof. Background technique [0002] The following descriptions of the background related to the present invention are provided to assist an understanding of the present invention and should not be considered as prior art to the present invention. All cited publications are incorporated by reference in their entirety. [0003] Tumor cells grow with blood vessels as the center. Cells that are more than 180 μm away from blood vessels are prone to form necrotic areas due to decreased oxygen concentration and lack of nutrients. The low oxygen concentration area at the front of the necrotic area is hypoxic tissue. Hypoxic cells account for about 10-50% of tumor cells. %, most of them are in the G0 phase of cell dynamics, showing no proliferation or slow proliferation,...

Claims

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Application Information

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IPC IPC(8): C07D401/14A61K31/517A61P35/00
CPCC07D401/14
Inventor 李祎亮魏会强李德冠唐卫生段玉清尚海花樊赛军
Owner INST OF RADIATION MEDICINE CHINESE ACADEMY OF MEDICAL SCI
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