The Pfitzinger Reaction. (Review)

Shvekhgeimer, M.-G. A.

doi:10.1023/b:cohc.0000028623.41308.e5

Cited by 78 publications

(19 citation statements)

References 52 publications

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“…The synthetic route to target compounds is outlined in Scheme 1. Commercially available isatin compounds 1a–b were first reacted with 4-bromoacetophenone ( 2 ) under basic conditions in refluxing ethanol to provide the intermediate 2-(4-bromophenyl)quinoline-4-carboxylic acids 3a–b according to the standard Pfitzinger reaction protocol [8]. Following construction of the quinoline framework, the carboxylic acid function was first esterified then reacted with hydrazine hydrate to provide the corresponding hydrazide derivatives 4a–b .…”

Section: Resultsmentioning

confidence: 99%

“…Elemental analysis (% CHN) was run by combustion analysis through an outsourced service (Medac Ltd, Surrey, UK). Commercial compounds were used as received; 2-(4-bromophenyl)quinoline-4-carboxylic acid ( 3a ) [20] and 2-(4-bromophenyl)-6-methoxyquinoline-4-carboxylic acid ( 3b ) [21] were accessed via the standard Pfitzinger reaction protocol [8].…”

Section: Methodsmentioning

confidence: 99%

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New Quinoline-Based Heterocycles as Anticancer Agents Targeting Bcl-2

et al. 2019

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The Bcl-2 protein has been studied as an anticancer drug target in recent years, due to its gatekeeper role in resisting programmed cancer cell death (apoptosis), and the design of BH3 domain mimetics has led to the clinical approval of Venetoclax (ABT-199) for the treatment of chronic lymphocytic leukaemia. In this work we extend our previous studies on the discovery of indole-based heterocycles as Bcl-2 inhibitors, to the identification of quinolin-4-yl based oxadiazole and triazole analogues. Target compounds were readily synthesized via a common aryl-substituted quinolin-4-carbonyl-N-arylhydrazine-1-carbothioamide (5a–b) intermediate, through simple variation of the basic cyclisation conditions. Some of the quinoline-based oxadiazole analogues (e.g. compound 6i) were found to exhibit sub-micromolar anti-proliferative activity in Bcl-2-expressing cancer cell lines, and sub-micromolar IC50 activity within a Bcl2-Bim peptide ELISA assay. The Bcl-2 targeted anticancer activity of 6i was further rationalised via computational molecular modelling, offering possibilities to extend this work into the design of further potent and selective Bcl-2 inhibitory heteroaromatics with therapeutic potential.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

New Quinoline-Based Heterocycles as Anticancer Agents Targeting Bcl-2

et al. 2019

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“…The Pfitzinger reaction of isatin on compounds containing the COCH 2 group is known to provide a convenient one-pot synthetic entry to quinoline-4-carboxylic acid derivatives. 11 It is reported 12 that enolizable ketones show great facility to condense with isatin in strongly alkaline medium to subsequently cyclize to give quinoline products. Application of this strategy on 9 and 10 allowed 12 and 13 to be formed in moderate to good yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of novel precursors of Pfitzinger reaction: A facile one-pot strategy to the synthesis of quinoline carboxylic acid derivatives of pyrazolo-carbazoles and azacarbazoles

2012

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Interaction of 5-indazolyldiazonium chloride 2 with 2-hydroxymethylidene cyclohexanone 5 and N-benzyl-3-hydroxymethylidene-4-piperidone 6 under the conditions of Japp-Klingemann reaction, followed by Fischer-indolization of the resulting hydrazones, formed the 5,7,8,9-tetrahydropyrazolo[4,3-b]carbazol-6(1H)-one 9 and 9-benzyl-5,7,8,9-tetrahydropyrido[2 ,3 :4,5]pyrrolo[2,3-f]indazol-6(1H)-one 10, respectively. Pfitzinger reaction of 9 and 10 with isatin in alkali afforded the corresponding quinoline carboxylic acid derivatives 12 and 13, respectively.

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“…Pfitzinger's own studies of the late nineteenth century indicate this reaction is generally efficient-he reported obtaining 2-methylquinoline-4-carboxylic acid in up to 80% yield [26]. However, there are also less-efficient examples of this reaction, owing to a thick resin surrounding the crude product and hampering isolation [27].…”

Section: Pfitzinger Reactionmentioning

confidence: 99%

Recent Advances in Metal-Free Quinoline Synthesis

2016

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Abstract:The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner-Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns.

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The Pfitzinger Reaction. (Review)

Cited by 78 publications

References 52 publications

New Quinoline-Based Heterocycles as Anticancer Agents Targeting Bcl-2

New Quinoline-Based Heterocycles as Anticancer Agents Targeting Bcl-2

Synthesis of novel precursors of Pfitzinger reaction: A facile one-pot strategy to the synthesis of quinoline carboxylic acid derivatives of pyrazolo-carbazoles and azacarbazoles

Recent Advances in Metal-Free Quinoline Synthesis

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