Chromeno[3',4':5,6]pyrano[2,3-b]quinoline derivative, preparation method and application thereof

A technology of derivatives and chromenes, applied in the field of organic synthesis, can solve the problem of difficult availability of synthetic raw materials, and achieve good effects of inhibiting proliferation and anti-tumor activity in vitro

Inactive Publication Date: 2017-08-29
JIANGSU UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The technical problem solved by the present invention is that the synthesis process of pyranoquinoline in the prior art requires noble metals as catalysts, and the defects that the sy...

Method used

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  • Chromeno[3',4':5,6]pyrano[2,3-b]quinoline derivative, preparation method and application thereof
  • Chromeno[3',4':5,6]pyrano[2,3-b]quinoline derivative, preparation method and application thereof
  • Chromeno[3',4':5,6]pyrano[2,3-b]quinoline derivative, preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0020] Add 2-chloroquinoline-3-carbaldehyde (0.2mmol), malononitrile (0.2mmol) and 4-hydroxycoumarin (0.2mmol) into a 5mL microwave reaction tube, then add L-proline (0.1 mmol ) and 2 mL of ethanol, seal the reaction tube, stir for 10 seconds in advance, and react the mixture at 100°C for 30 minutes under microwave radiation. A mixed solvent of water was recrystallized to obtain 2-(6-oxo-6,7-dihydrochromeno[3',4':5,6]pyrano[2,3-b]quinoline-7 -yl) malononitrile (Ia): yield 71%; m.p.: 274-276 °C; IR (KBr, ν, cm -1 ):2917,2250,1701, 1638,1607,1493,1404,1332,1244,1204,1169,1151,1050,1025,987, 769,754; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):8.84(s,1H,ArH),8.15(d,J=8.0Hz,2H,ArH),8.04(d,J=8.4Hz,1H,ArH),7.94-7.90(m, 1H, ArH), 7.86-7.82(m, 1H, ArH), 7.70(t, J=7.6Hz, 1H, ArH), 7.61(d, J=8.4 Hz, 1H, ArH), 7.57(t, J= 8.0Hz,1H,ArH),5.38(d,J=4.0Hz,1H,CH),5.34 (d,J=3.6Hz,1H,CH). 13 C NMR (100MHz, DMSO-d 6 )(δ,ppm):162.3, 160.0,158.5,153.7,152.6,145.6,140.8,134.0,131.9,128.3,127.6,127.0,126...

Embodiment 2

[0022] According to the method for embodiment 1, 2-chloroquinoline-3-formaldehyde is changed into 6-methoxyl group-2-chloroquinoline-3-formaldehyde, with L-proline as catalyst, reacted under microwave radiation for 30 minutes, After the reaction, the reaction system was cooled to room temperature, and after the solid was precipitated, suction filtration was performed, and the target product 2-(10-methoxy-6-oxo-6,7-di Hydrochromeno[3',4':5,6]pyrano[2,3-b]quinolin-7-yl)malononitrile (Ib): Yield 75%; m.p.: 258-260°C ;IR(KBr,ν,cm -1 ):2903,2254,1686,1637,1609,1497,1455, 1353,1236,1172,1113,1025,1005,993,794,747; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):8.69(s,1H,ArH),8.14-8.11(m,1H,ArH),7.94(d,J=9.2Hz,1H,ArH),7.85-7.81(m,1H,ArH ),7.61-7.53(m,4H,ArH),5.35(d, J=3.6Hz,1H,CH),5.31(d,J=3.6Hz,1H,CH),3.94(s,3H,CH 3 o). 13 C NMR (75MHz, DMSO-d 6 )(δ,ppm):160.5,159.0,158.1,153.1,152.6,141.7, 139.6,134.4,129.5,128.6,125.7,124.9,123.4,117.4,113.7,113.6, 113.2,112.9,106.3,5.6,98 , 30.8. HRMS...

Embodiment 3

[0024]According to the method for Example 1, 2-chloroquinoline-3-formaldehyde is replaced with 6-tert-butyl-2-chloroquinoline-3-formaldehyde, and L-proline is used as a catalyst to react under microwave radiation for 30 minutes, After the reaction, the reaction system was cooled to room temperature, and after the solid was precipitated, suction filtration was performed, and the target product 2-(10-tert-butyl-6-oxo-6,7-di Hydrochromeno[3',4':5,6]pyrano[2,3-b]quinolin-7-yl)malononitrile (Ic): Yield 73%; m.p.: 284-286℃ ;IR(KBr,ν,cm -1 ):2963,2255,1702,1640,1610,1497,1460, 1438,1396,1380,1366,1271,1183,1169,1150,1126,1098,988,969, 915,831; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):8.82(s,1H,ArH),8.17(d,J=7.6Hz,1H,ArH),8.09-8.00(m,3H,ArH),7.86(t,J=8.0Hz, 1H, ArH),7.64-7.58(m,2H,ArH),5.38(d,J=3.6Hz,1H,CH),5.34(d,J=3.6Hz,1H,CH),1.45(s,9H, (CH 3 ) 3 C). 13 C NMR (75MHz, DMSO-d 6 )(δ,ppm): 160.5,158.9,153.9,153.1,150.0,144.5,141.1,134.5,131.4,127.7, 127.1,125.7,123.4,117.4,113.7,113....

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Abstract

A chromeno[3',4':5,6]pyrano[2,3-b]quinoline derivative is represented as the structure formula (I), wherein R1 is any one from H, CH3O, Cl or (CH3)3C; R2 is H or CH3; and R3 is H, CH3 or Ph. The derivative is prepared through one step with 2-chloroquinoline-3-formaldehyde or a derivative thereof, malononitrile and 4-hydroxycoumarin as raw materials, which are simple and are easy to obtain. The method has mild conditions and reaches 75% in total yield. A pharmacological test proves that the compound has excellent in-vitro proliferation inhibiting effect to human hepatoma cell line HepG2, so that the compound can inhibit growth of tumor cells and can be applied to preparation of antitumor medicines.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and relates to a preparation method of chromeno[3',4':5,6]pyrano[2,3-b]quinoline derivatives and their application in antitumor drugs Background technique [0002] Chromene, also known as benzopyran, its skeleton widely exists in natural products, for example, vitamin E, flavonoids, isoflavones, etc. all contain chromene skeleton. Chromene derivatives have a wide range of biological and pharmacological activities. There have been reports of anti-allergic and anti-cancer activities. [0003] Quinoline, also known as benzopyridine or aziridine, is a very important class of nitrogen-containing heterocyclic compounds, especially in the pharmaceutical industry and has a wide range of applications. Moreover, they are also the mother nucleus of the structure of many natural products and bioactive drugs, such as: chloroquine, camelline, camptothecin. After continuous research by pharmacologi...

Claims

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Application Information

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IPC IPC(8): C07D491/153A61P35/00
CPCC07D491/153
Inventor 林伟蔡琦胡秀秀王雅珍王赟
Owner JIANGSU UNIV OF TECH
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