Quinoline derivatives, their preparation and use

A derivative, quinoline technology, applied in the field of quinoline-2-carboxylate derivatives, preparation and pharmaceutical compositions containing such derivatives, can solve the inability to eradicate cancer cells, infertility, side effects, etc. question

Active Publication Date: 2017-06-06
FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Surgical treatment sometimes fails to eradicate cancer cells, so that the cancer cells continue to spread and recur; in addition, surgical treatment may also lead to serious consequences, such as cervical cancer and bladder cancer surgery may lead to infertility and sexual dysfunction; Damages normal cells; therefore drug treatment is a better option for cancer
However, due to the continuous emergence of multidrug resistance, the treatment of cancer is difficult
In addition: the current clinically used anticancer drugs still cannot achieve a satisfactory level of specificity. When a patient undergoes chemotherapy, normal cells in the body are often also poisoned, seriously affecting normal physiological functions, and often with many side effects

Method used

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  • Quinoline derivatives, their preparation and use
  • Quinoline derivatives, their preparation and use
  • Quinoline derivatives, their preparation and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 Synthesis of intermediate 3-substituted phenyl-5-hydroxymethyl-isoxazole (II) or intermediate 3-substituted phenyl-5-aminomethyl-isoxazole (III):

[0061] Using substituted benzaldehyde as raw material, it is prepared by synthesis of oxime, 1,3-dipolar cycloaddition reaction, methylsulfonyl esterification reaction, azidation, and reduction reaction (R and n are as above), see the following process for details :

[0062]

[0063] For the specific synthesis process of intermediate 3-substituted phenyl-5-hydroxymethyl-isoxazole (II) or intermediate 3-substituted phenyl-5-aminomethyl-isoxazole (III), please refer to the applicant The publication numbers of the previous applications are three applications of CN103360382A, CN103664991A and CN103601762A, the full text of which is incorporated herein by reference.

Embodiment 2

[0064] Synthesis of quinoline derivatives (I-1) shown in embodiment 2 formula (I):

[0065] Where R is H as an example to illustrate:

[0066] Synthesis of [(3-phenyl-isoxazol-5-yl)-methyl]-quinoline-2-carboxylate (YQ-1)

[0067]

[0068] Add 0.167g (1mmol) of quinoline-2-carboxylic acid and 0.206g (1mmol) of DCC into a 50mL round bottom flask, add 10mL of dry THF, and stir in an ice bath for 30min to dissolve 0.175g (1mmol) of 5-hydroxymethyl A 10 mL THF solution of 1-3-phenyl-isoxazole and 0.122 g (1 mmol) DMAP was slowly added dropwise to the reaction system, stirred in an ice bath for 30 min, and then naturally rose to room temperature for reaction. After the completion of the TLC detection reaction, the reaction solution was concentrated in vacuo, and the residue was directly column-separated [V (petroleum ether): V (ethyl acetate) = 5:1~2:1] to obtain the target compound [(3-phenyl-isoxane (Azol-5-yl)-methyl]-quinoline-2-carboxylate (YQ-1). The rest of the compound...

Embodiment 3

[0069] Synthesis of quinoline derivatives (I-2) shown in embodiment 3 formula (I):

[0070] where R is H as an example to illustrate

[0071] Synthesis of N[(3-phenyl-isoxazol-5-yl)-methyl]-quinoline-2-carboxamide (YQ-20)

[0072]

[0073] Add 0.167g (1mmol) of quinoline-2-carboxylic acid, 0.206g (1mmol) of DCC and 0.135g (1mmol) of HOBT into a 50mL round bottom flask, add 10mL of dry THF, and stir in an ice bath for 30min to dissolve 0.174g (1mmol) 5-aminomethyl-3-phenyl-isoxazole and 0.122g (1mmol) DMAP in 10mL THF solution were slowly added dropwise to the reaction system, stirred in an ice bath for 30min, and then naturally rose to room temperature for reaction. After the reaction was detected by TLC, the reaction solution was concentrated in vacuo, and the residue was directly column separated [V (petroleum ether): V (ethyl acetate) = 5:1~2:1] to obtain the target compound N[(3-phenyl-iso Oxazol-5-yl)-methyl]-quinoline-2-carboxamide (YQ-20). The rest of the compound...

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Abstract

The invention discloses a quinoline derivative as shown in the formula (I) in the specification and a salt of the quinoline derivative, wherein in the formula, Z is NH or O; R is selected from hydrogen, fluorine, chlorine, bromine, methyl, ethyl, tertiary butyl, trifluoromethyl, methoxyl or nitryl; n is an integer of 0, 1, 2 or 3. The invention relates to a preparation method and application of the compound as shown in the formula (I) in the specification and the salt of the compound. The compound or the salt has very high inhibition activity for a human lung cancer cell strain A549, a colorectal cancer cell strain HCT-116 and a breast cancer cell strain MCF-7. The compound has a broad-spectrum anti-cancer activity and can be used as a candidate medicine or a lead compound for treating diseases such as tumor and cancer.

Description

technical field [0001] The invention belongs to the field of medicine and relates to a class of novel quinoline derivatives, in particular to quinoline-2-formic acid ester derivatives (I-1) and quinoline-2-carboxamides containing an isoxazole heterocycle Preparation of derivative (I-2), pharmaceutical composition containing such derivative and use thereof. [0002] The compounds or their salts have strong inhibitory activity on human lung cancer cell line A549, colon cancer cell line HCT-116 and breast cancer cell line MCF-7. The compounds have broad-spectrum anticancer activities and can be used as candidate drugs or lead compounds for treating diseases such as tumors and cancers. Background technique [0003] Cancer is a large class of diseases characterized by abnormal cell proliferation and metastasis, and is the second leading cause of death in humans, second only to cardiovascular and cerebrovascular diseases. Cancer can occur in various organs and tissues at any age...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D413/12A61K31/4709A61P35/00
CPCY02P20/55
Inventor 雍建平卢灿忠
Owner FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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