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Quinolin-4-carboxamide derivative and medicinal use thereof

A formamide and derivative technology, applied in the field of medicine, can solve the problems of unclear drug efficacy, pharmacology and incompatibility, high safety, and reduced potential risks.

Inactive Publication Date: 2015-06-17
CHENGDU MILITARY GENERAL HOSPITAL OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing serotonin reuptake inhibitory drugs and dopamine D2 receptor antagonists are two drugs with different mechanisms of action, and their efficacy, pharmacology and incompatibility are not yet clear when they are used in combination. Moreover, for the treatment of diseases, The potential risk of using a single drug will be reduced and the safety will be higher

Method used

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  • Quinolin-4-carboxamide derivative and medicinal use thereof
  • Quinolin-4-carboxamide derivative and medicinal use thereof
  • Quinolin-4-carboxamide derivative and medicinal use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Preparation of (N-{3-[4-(5-chloro-2-methylphenyl)piperazinyl]propyl}-quinoline-4-carboxamide, compound 1)

[0057] (1) Quinoline-2,4-dicarboxylic acid: take isatin 1.0g (6.75mmol), pyruvic acid 0.7g (8.10mmol) and dissolve in 25ml concentration of 20% NaOH solution, set the microwave power to 110W, React for 10 minutes, stop the reaction, cool to room temperature, acidify with 1M hydrochloric acid solution to a Ph value of about 2, a yellow solid precipitates, filter the solid with suction, wash thoroughly with water, and dry at 60°C for 12 hours to obtain the crude product of quinoline-2,4-dicarboxylic acid , dissolved in hot water, decolorized with activated carbon, filtered, and recrystallized to obtain 1.30 g of pure quinoline-2,4-carboxylic acid, with a yield of 89.2%. Mp: 235-240°C. 1 H NMR (DMSO-d6): δ=8.81(d, J=7.6Hz, 1H), 8.48(s, 1H,), 8.26(d, J=7.8Hz, 1H), 7.95(m, 1H), 7.86 (m,1H).

[0058] (2) Quinoline-4-carboxylic acid: Weigh 1.1 g (5.1 mmol) of quinolin...

Embodiment 2

[0063] Preparation of N-{3-[4-(5-chloro-2-methylphenyl)piperazinyl]propyl}-5-fluoroquinoline-4-carboxamide (compound 2)

[0064] (1) 5-Fluoro-quinoline-4-carboxylic acid: According to the method of Example 1, 4-fluoroisatin was prepared by microwave-catalyzed Pfitzinger reaction with pyruvic acid under alkaline conditions. Yield 83.4%, Mp: 265-269°C. 1 H NMR (DMSO-d6): δ=9.12(d, J=4.5Hz, 1H), 8.73(d, J=8.7Hz, 1H), 8.19(d, J=8.4Hz, 1H), 8.0(d, J=4.5Hz, 1H), 7.89-7.79 (m, 1H).

[0065] (2) N-{3-[4-(5-chloro-2-methylphenyl) piperazinyl] propyl group}-5-fluoroquinoline-4-formamide: according to the method of Example 1, get 5-Fluoroquinoline-4-carboxylic acid to prepare 5-fluoroquinoline-4-formyl chloride, and then react with 3-[4-(5-chloro-2-methylphenyl)piperazinyl]propylamine, after deacidification prepared by acylation in the presence of sodium carbonate. Yield: 80.1%, Mp: 263-265°C. 1 H NMR (CDCl 3 ):δ=1.64(m,2H),2.23(s,3H),3.10-3.22(m,4H),3.39(m,2H),3.55(m,2H),7.07(t,J=...

Embodiment 3

[0067] Preparation of N-{3-[4-(5-chloro-2-methylphenyl)piperazinyl]propyl}-5-trifluoromethylquinoline-4-carboxamide (Compound 3)

[0068] According to the method of Example 1, take 5-trifluoromethyl-quinoline-4-formic acid to prepare 5-trifluoromethyl-quinoline-4-formyl chloride, and then combine with 3-[4-(5-chloro-2 -Methylphenyl) piperazinyl] propylamine reaction, prepared by acylation in the presence of acid-removing agent sodium carbonate. Yield: 82.7%. 1 H NMR (DMSO-d6): δ=1.47(br-s,2H),1.52(br-s,2H),2.36(s,3H),3.38(br-m,4H),3.29(q,J= 5.00Hz, 2H), 3.35(d, J=8.05Hz, 2H), 7.15(m, 2), 7.26(d, J=6.80Hz, 1H), 7.24(d, J=8.10Hz, 1H), 7.58 (d,J=1.92Hz,1H),7.73(dd,J 1 =8.22Hz,J 2 =1.62Hz, 1H), 8.43(br-s, 1H, NH), 9.85(br-s, 1H).

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Abstract

The invention discloses a quinolin-4-carboxamide derivative. The quinolin-4-carboxamide derivative is a compound with the structure represented by formula I shown in the specification, and the phenyl ring of the compound has at least one substituent group; the substituent group is selected from halogen, -CF3, C1-C4 alkyl groups, C1-C4 alkyloxy groups, and C1-C4 alkyl substituent groups; and n is an integer in a range of 1-4. The compound has 5-hydroxytryptamine reuptake inhibition and dopamine D2 receptor antagonism dual functions, and can be used for preventing and treating PTSD.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a quinoline-4-carboxamide derivative and the application of the compound in medicine for treating post-traumatic stress disorder. Background technique [0002] Posttraumatic stress disorder (Posttraumatic Stress Disorder, PTSD) is a morbid mental reaction to severe traumatic events (such as combat trauma, traffic accidents, violent crimes, terrorist attacks, major infectious disease epidemics, and natural disasters, etc.) . According to the American Psychiatry Association (American Psychiatry Association, APA) statistics, the overall prevalence of PTSD in the United States is 1-14%, with an average of 8%, and the individual's lifetime risk of disease is 3-58%. 2 times that of men. According to statistics from the Institute of Psychology of the Chinese Academy of Sciences, six months after the Wenchuan earthquake, 12.7%-22.1% of the population suffered from post-traumatic stress disorder...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/50A61K31/496A61P25/00A61P25/18
CPCC07D215/50
Inventor 顾建文祝辉匡永勤马原杨涛张新颜李运明
Owner CHENGDU MILITARY GENERAL HOSPITAL OF PLA