- Synthesis method and device of 4 -hydroxyquinoline -3 - formic acid
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The invention relates to the technical field of medicine preparation, and particularly discloses a synthesis method and device of 4 -hydroxyquinoline -3 - formic acid, wherein o-nitrobenzoic acid and a monoethyl propionate potassium salt are condensed to obtain 3 - (2 - nitrophenyl) -3 - oxopropanoate. The ethyl powder is reacted with 3 - (2 - nitrophenyl) -3 - oxopropanoate to obtain 3 - (2 - aminophenyl) -3 - oxopropanoate. 3 - (2 - Aminophenyl) -3 - oxopropanoate was reacted with DMF-DMA and DMF via a closed loop to give 4 -hydroxyquinoline -3 - ethyl ester. The 4 -hydroxyquinoline -3 - formate was hydrolyzed under basic conditions to give 4 -hydroxyquinoline -3 - formic acid. 4 -hydroxyquinoline -3 - formic acid has the advantages of low cost, short reaction time and simple post-treatment in the synthesis process.
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Paragraph 0072-0077; 0112
(2021/09/21)
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- Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
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Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
- Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
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p. 2214 - 2231
(2020/03/06)
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- An Efficient Synthesis of Ivacaftor
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New and practical synthetic route of ivacaftor is described on a grams scale. An electrophilic addition of two t-butyl groups to the aromatic ring is adopted to prepare 5-amino-2,4-di-t-butylphenol in 61% yield over three steps with 98.1% purity (high-performance liquid chromatography). An intramolecular cyclization of ethyl 3-(2-aminophenyl)-3-oxo-propanoate with dimethylformamide-dynamic mechanical analysis is used to prepare 4-oxo-1,4-dihydroquinoline-3-carboxylic acid in 54% yield over four steps. Ivacaftor is obtained by condensation of the two parts in 71% yield with 99.1% purity (high-performance liquid chromatography).
- Zhang, Rui,Han, Guanyu,Jiang, Luobin,Shen, Yao,Yang, Rui,Mao, Yongjun,Wang, Hang
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p. 3169 - 3173
(2017/10/05)
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- Preparation method of 4-hydroxyquinoline-3-carboxylic acid
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The invention relates to the technical field of organic synthesis and bulk drug intermediates, and concretely relates to a preparation method of a key intermediate 4-hydroxyquinoline-3-carboxylic acid of a new medicine ivacaftor for treating cystic fibrosis. The preparation method comprises the following steps: 1, carrying out a condensation reaction: reacting o-nitrobenzoic acid, potassium monoethyl malonate and N,N-carbonyldiimidazole to prepare ethyl 3-(2-nitrophenyl)-3-oxopropanoate; 2, carrying out a reduction reaction: carrying out catalytic hydrogenation reduction on ethyl 3-(2-nitrophenyl)-3-oxopropanoate to prepare ethyl 3-(2-aminophenyl)-3-oxopropanoate; 3, carrying out a cyclization reaction: carrying out nucleophilic addition and cyclization reaction on ethyl 3-(2-aminophenyl)-3-oxopropanoate and N,N-dimethyl formamide dimethyl acctel to obtain ethyl 4-hydroxyquinoline-3-carboxylate; and 4, carrying out a hydrolysis reaction: carrying out the hydrolysis reaction on ethyl 4-hydroxyquinoline-3-carboxylate to obtain 4-hydroxyquinoline-3-carboxylic acid. The preparation method has the advantages of easily available raw materials, mild reaction conditions, simplicity and convenience in post-treatment, suitableness for amplified preparation, and high yield.
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Paragraph 0015; 0035; 0036; 0037; 0038; 0039; 0040
(2017/02/09)
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- Expeditious synthesis of ivacaftor
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An expeditious synthesis for Ivacaftor featuring modified Leimgruber-Batcho procedure was described. The overall yield is 39% over six steps from commercially available 2-nitrobenzoyl chloride.
- He, Yang,Xu, Qien,Ma, Wenpeng,Zhang, Jian,Sun, Hongbing,Shen, Jingshan
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p. 1035 - 1040
(2014/04/17)
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- Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido[5,4-c] quinoline derivatives
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A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro. It was found that most of the tested compounds especially compound 17, s
- Zhang, Fan,Zhai, Xin,Chen, Li Juan,Qi, Jian Guo,Cui, Bo,Gu, Yu Cheng,Gong, Ping
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p. 1277 - 1280
(2012/01/06)
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- Novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole compounds
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Certain 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indoles are 5-HT ligands and are useful for treating diseases wherein modulation of 5-HT activity is desired.
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- A novel trifluoromethanesulfonamidophenyl-substituted quinoline derivative, GA 0113: Synthesis and pharmacological profiles
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The trifluoromethanesulfonamidophenyl-substituted quinoline GA 0113 have been synthesized from o-nitrobenzoyl chloride via a multi-step process. GA 0113 displaced specific binding of [125I]-Sar1, Ile8-Ang II to AT1 receptors in membrane from Sf9 cells. In concious normotensive dogs, GA 0113 inhibited the Ang II-induced pressor response with ID50 of 0.032mg/kg and dose-dependently increased plasma renin activity for 48h.
- Morizawa, Yoshitomi,Okazoe, Takashi,Wang, Shu-Zhong,Sasaki, Jun,Ebisu, Hajime,Nishikawa, Masakuni,Shinyama, Hiroshi
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- 2-arylquinolines and process for producing the same
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2-Arylquinolines represented by formula (1): STR1 wherein R 1, R 3 to R 9 each represents hydrogen, halogen, lower alkyl, cyclic lower alkyl, aryl, aralkyl, alkoxy or --C m F 2m+1 ; R 2 represents hydrogen, halogen, lower alkyl, cyclic lower alkyl, aryl,
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- Dibenzo[1,6]naphthyridindiones as modified quinolone antibacterials
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A series of dibenzo[1,6]naphthyridindiones, synthesized as modified quinolones, in which the usual carboxylic group was replaced by a heterocyclic amide function, was evaluated for antibacterial activity. None of the target compounds showed any significant antibacterial activity. Semiempirical molecular orbital AM1 calculations allowed us to hypothesize that the lack of activity could depend on amide tautomeric equilibrium.
- Cecchetti, Violetta,Fravolini, Arnaldo,Sabatini, Stefano,Tabarrini, Oriana,Xin, Tao
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p. 899 - 903
(2007/10/03)
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- Pyrazoloquinolines
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2-Aryl-pyrazolo[4-3-c]quinolin-3-ones, e.g. those of the formula STR1 and pharmaceutically acceptable acyl derivatives or salts thereof, are psychoactive agents useful in the treatment of anxiety or depression.
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