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Design, synthesis and application of quinolinone fumaramide derivatives

A kind of technology of phenyl fumarate and tetrahydroquinoline, applied in the field of chemistry

Inactive Publication Date: 2020-01-21
SOUTHWEST UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] So far, the novel compounds involved in the present invention have not been reported in terms of inhibiting the activity of chitin synthase, so they are used as chitin synthase inhibitors and developed into novel antifungal preparations for human health. make a greater contribution

Method used

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  • Design, synthesis and application of quinolinone fumaramide derivatives
  • Design, synthesis and application of quinolinone fumaramide derivatives
  • Design, synthesis and application of quinolinone fumaramide derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: the preparation of aniline chalcone 3a:

[0028] Maleic anhydride (2.37g, 24.16mmol) was dissolved in 60ml of anhydrous dichloromethane, aniline (2ml, 21.96mmol) was added, and the mixture was stirred at room temperature for 2 hours, a white precipitate was formed, filtered and distilled Wash with methyl chloride to obtain a pure solid, white powder; the synthesis method of compound 3b-s is the same as that in Example 1.

Embodiment 2

[0029] Example 2: N 1 -(2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)-N 4 -Synthesis of (o-tolyl)fumaramide) (1a)

[0030] Add CH to a 50 mL round bottom flask 2 Cl 2 (30 mL), add triethyl phosphite (0.44ml, 2.5 mmol) under ice-water bath, I 2 (0.636g, 2.5 mmol), add acid (0.510g, 2.5mmol) and triethylamine (1.74ml, 12.5mmol) after the iodine element is completely dissolved, after stirring for 20 min, add compound amine (0.487g, 3.0mmol) dropwise , remove the ice-water bath, react at room temperature for 3 hours, and detect the reaction by TLC spot plate. After the reaction is completed, remove the solvent by rotary evaporation, add 50ml ethyl acetate, wash with 1M HCl (30ml×3), and then wash with saturated sodium bicarbonate solution (30ml ×3), using anhydrous sodium sulfate to remove water, and rotary evaporation to remove the solvent to obtain a white solid, which was recrystallized with methanol / ethyl acetate to obtain the pure target compound with a yield of 80%. The phys...

Embodiment 3

[0031] Example 3: N 1 -(2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)-N 4 -Synthesis of (m-tolyl)fumaramide (1b)

[0032] The synthetic method of compound 1b is the same as above, and the physical constants and spectral data of 1b are as follows:

[0033] 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.01 (s, 1H CONH ), 10.41 (s, 1H CONH ),9.12 (s, 1H CONH ), 7.47-7.38 (m, 2H Ar-H ), 7.25-7.14 (m, 3H Ar-H), 6.95 (t, J =7.4 Hz, 1H Ar-H ), 6.89 (d, J = 7.7 Hz, 2H Ar-H ), 6.37 (s, 2H CH=CH), 4.62- 4.50 (m, 1H quinoline-CH ), 3.18-3.08 (m, 1H), 2.97-2.86 (m, 1H), 2.28 (s,3H Ar-CH 3 ). 13 C NMR (101 MHz, DMSO-d 6 ) δ 168.64, 165.06, 163.79, 139.16,138.42, 137.90, 134.30,130.42, 129.07, 128.63, 128.07, 124.76,122.79, 122.70,120.34, 117.09, 115.63, 48.63, 31.66, 21.64. HRMS (ESI): calcd for C 20 h 19 N 3 NaO 3 [M+Na] + , 372.1319, found, 372.1318.

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Abstract

The invention discloses design, synthesis and application of an N1-(2-oxo-1,2,3,4-tetrahydroquinoline-3-yl)-N4-phenyl fumamide compound. The structure of the compound is shown as a general formula I,wherein R is hydrogen, methyl, ethyl, methoxyl and the like. Bioactivity test experiments prove that the compound has obvious inhibitory activity on chitin synthase, has good inhibitory activity on fungi such as candida albicans, aspergillus flavus, cryptococcus neoformans and aspergillus fumigatus, and can be used for preparing antifungal drugs.

Description

technical field [0001] The invention belongs to the field of chemistry and relates to novel 3-amino-3,4-dihydroquinolin-2(1H)-one compounds, in particular to a N 1 -(2-Oxo-1,2,3,4-tetrahydroquinolin-3-yl)-N 4 - Design, synthesis and application of phenyl fumaramide compounds. Background technique [0002] Fungal infection is a major threat to human health, especially the incidence of deep fungal infection in immunocompromised populations remains high, and the resulting mortality rate has also increased sharply in recent years. At present, there are five main antifungal drugs clinically, including echinocandins (such as caspofungin), polyenes (such as amphotericin B), azoles (such as itraconazole), pyrimidines (such as flucytosine) and acrylamides (such as terbinafine). Due to the potential toxicity and side effects of these drugs, as well as the emergence of drug-resistant fungi, the treatment effect on deep fungal infections is not satisfactory, and there is an urgent ne...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/38A61K31/4704A61P31/04A61P31/10
CPCC07D215/38A61P31/04A61P31/10Y02A50/30
Inventor 吉庆刚李百慧
Owner SOUTHWEST UNIVERSITY
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