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Quinoline derivative containing furyl and preparation method and application thereof

A technology of alkyl group and group is applied in the field of quinoline derivatives containing furanyl group and preparation thereof, and can solve the problems of high non-selectivity, acute toxicity or cell drug resistance of antitumor drugs

Active Publication Date: 2021-05-07
河南省医药科学研究院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, anti-tumor drugs generally have the defects of non-selectivity, acute toxicity or high cell drug resistance

Method used

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  • Quinoline derivative containing furyl and preparation method and application thereof
  • Quinoline derivative containing furyl and preparation method and application thereof
  • Quinoline derivative containing furyl and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] Example 1: (E)-N-(4-(4-(benzyloxy)anilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(furan-2- base) the synthesis of acrylamide (a)

[0099]

[0100] (1) Synthesis of trans-3-(2-furyl)acryloyl chloride (a-1)

[0101] Add trans-3-(2-furyl)acrylic acid into a 50mL three-necked flask equipped with a thermometer and electromagnetic stirring

[0102] (0.003mol, 0.41g), 7mL thionyl chloride, reflux reaction under nitrogen protection for 4h, the remaining solvent was evaporated under reduced pressure, and the solvent was removed under reduced pressure to obtain 0.44g of light yellow oil with a yield of 95.0%.

[0103] (2) Synthesis of N-(4-(4-(benzyloxy)anilino)-3-cyano-7-ethoxyquinolin-6-yl)acetamide (a-2)

[0104] Add N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide (0.024mol, 6.90g) into a 500mL three-necked flask equipped with a thermometer and electromagnetic stirring, 4- (Benzyloxy) aniline (0.026mol, 5.17g) and (0.026mol, 3.0g) pyridine hydrochloride, 250mL isopropanol, ...

Embodiment 2

[0114] Example 2: (E)-N-(4-(4-chloroanilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(furan-2-yl)acrylamide Synthesis of (b)

[0115]

[0116] (1) Synthesis of N-(4-(4-chloroanilino)-3-cyano-7-ethoxyquinolin-6-yl)acetamide (b-1)

[0117] According to the method of step (2) in Example 1, add N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl) in a 500mL three-necked flask equipped with a thermometer and electromagnetic stirring Acetamide (0.024mol, 6.90g), 4-chloroaniline (0.026mol, 3.30g), and (0.026mol, 3.00g) pyridine hydrochloride, 250mL isopropanol, TLC tracking detection, developing solvent is petroleum ether: The volume ratio of ethyl acetate was 1:1, stirred and refluxed for 12h, allowed to stand, filtered with suction, and recrystallized from methanol to obtain intermediate b-1 (7.90g, 87%).

[0118] 1 H NMR (DMSO-d 6 ):δ11.09(br,s,1H),9.62(s,1H),9.08(s,1H),9.01(s,1H),7.62(s,1H),7.53-7.56(m,2H), 7.44-7.47(m,2H),4.33(q,J=6.8Hz,2H),2.11(s,3H),1.50(t,J=6.8Hz,3H)

[0119] (2) Syn...

Embodiment 3

[0126] Example 3: (E)-N-(4-(4-(3-fluorobenzyloxy)-3-chloroaniline)-3-cyano-7-ethoxyquinolin-6-yl)-3 Synthesis of -(furan-2-yl)acrylamide (c)

[0127]

[0128](1) N-(4-(4-(3-fluorobenzyloxy)-3-chloroaniline)-3-cyano-7-ethoxyquinolin-6-yl)acetamide (c-1) Synthesis

[0129] According to the method of step (2) in Example 1, add N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl) in a 500mL three-necked flask equipped with a thermometer and electromagnetic stirring Acetamide (0.024mol, 6.90g), 4-(3-fluorobenzyloxy)-3-chloroaniline (0.026mol, 6.53g) and (0.026mol, 3.0g) pyridine hydrochloride, 250mL isopropanol, TLC tracking detection, the developer is a mixture of petroleum ether: ethyl acetate with a volume ratio of 1:1, stirred and refluxed for 12 hours, allowed to stand, filtered with suction, and recrystallized from methanol to obtain intermediate c-1 (10.52g, 87%).

[0130] 1 H NMR (DMSO-d 6 ):δ11.09(br,s,1H),9.62(s,1H),8.98-9.10(m,2H),7.59-7.63(m,2H),7.27-7.50(m,5H),7.17-7.21(...

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Abstract

The invention belongs to the field of anti-cancer drugs, and particularly relates to a furyl-containing quinoline derivative and a preparation method and application thereof. The invention provides a compound as shown in the formula I, and a stereoisomer or pharmaceutically acceptable salt thereof. Compared with an existing antitumor drug, the compound disclosed by the invention has excellent antitumor activity on A431, SKOV3, SK-BR-3, BT474 and the like, and has a very good application prospect. In addition, the preparation method of the compound is low in cost, simple in step, mild in reaction condition, high in yield and easy for post-treatment.

Description

technical field [0001] The invention belongs to the field of anticancer drugs, and in particular relates to a furyl-containing quinoline derivative and its preparation method and application. Background technique [0002] Cancer is the second leading cause of death in the world after cardiovascular disease. Chemotherapy is one of the main treatments to inhibit tumor growth and metastasis. However, many patients face various side effects during chemotherapy or acquire resistance after a period of treatment. Medicine, the disease relapsed again. Therefore, the development of new antitumor agents is still a long way to go. [0003] Protein tyrosine kinases catalyze the phosphorylation of specific tyrosyl residues in various proteins involved in the regulation of cell growth and differentiation. Protein tyrosine kinases can be broadly classified as receptor (eg, EGFR, HER2 (C-ERB-2), C-MET, TIE-2, PDGFR, FGFR) or non-receptor (eg, C-SRC, LCK, ZAP70) kinase. Inappropriate or ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D405/12A61K31/4709A61P35/00A61P35/02
CPCC07D405/12A61P35/00A61P35/02
Inventor 邹敏金波郑立运李佳雯王明升王强方先珍张壮丽夏书梼黄小婉郭桐张晓
Owner 河南省医药科学研究院
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