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Keywords = Conrad–Limpach reaction

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15 pages, 1465 KB  
Article
Synthesis and Transformation of Tricyclic KYNA Derivatives
by Julián Robin Sárik, István Szatmári and Bálint Lőrinczi
Int. J. Mol. Sci. 2025, 26(13), 6248; https://doi.org/10.3390/ijms26136248 - 28 Jun 2025
Viewed by 704
Abstract
Kynurenic acid (KYNA) derivatives condensed with an aromatic ring (tricyclic KYNA derivatives) have been successfully synthesized, and the reactivity of these analogues has been investigated in the modified Mannich reaction resulting in new Mannich bases. The N,N-dimethyl-ethylenediamine analogues of the tricyclic KYNA [...] Read more.
Kynurenic acid (KYNA) derivatives condensed with an aromatic ring (tricyclic KYNA derivatives) have been successfully synthesized, and the reactivity of these analogues has been investigated in the modified Mannich reaction resulting in new Mannich bases. The N,N-dimethyl-ethylenediamine analogues of the tricyclic KYNA derivatives have also been successfully synthesized, and their reactivity in the modified Mannich reaction was investigated. The synthesized ring systems bear resemblance to molecules previously investigated as G-quadruplex binding agents. Based on this similarity, the synthesized tricyclic KYNA derivatives could be investigated as potential antiviral and anticancer molecules. Full article
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17 pages, 1923 KB  
Article
Synthesis of 4-Hydroxyquinolines as Potential Cytotoxic Agents
by Oszkár Csuvik, Nikoletta Szemerédi, Gabriella Spengler and István Szatmári
Int. J. Mol. Sci. 2022, 23(17), 9688; https://doi.org/10.3390/ijms23179688 - 26 Aug 2022
Cited by 4 | Viewed by 3762
Abstract
The synthesis of alkyl 2-(4-hydroxyquinolin-2-yl) acetates and 1-phenyl-4-(phenylamino)pyridine-2,6(1H,3H)-dione was optimised. Starting from 4-hydroxyquinolines (4HQs), aminomethylation was carried out via the modified Mannich reaction (mMr) applying formaldehyde and piperidine, but a second paraformaldehyde molecule was incorporated into the [...] Read more.
The synthesis of alkyl 2-(4-hydroxyquinolin-2-yl) acetates and 1-phenyl-4-(phenylamino)pyridine-2,6(1H,3H)-dione was optimised. Starting from 4-hydroxyquinolines (4HQs), aminomethylation was carried out via the modified Mannich reaction (mMr) applying formaldehyde and piperidine, but a second paraformaldehyde molecule was incorporated into the Mannich product. The reaction also afforded the formation of bisquinoline derivatives. A new 1H-azeto [1,2-a]quinoline derivative was synthesised in two different ways; namely starting from the aminomethylated product or from the ester-hydrolysed 4HQ. When the aldehyde component was replaced with aromatic aldehydes, Knoevenagel condensation took place affording the formation of the corresponding benzylidene derivatives, with the concomitant generation of bisquinolines. The reactivity of salicylaldehyde and hydroxynaphthaldehydes was tested; under these conditions, partially saturated lactones were formed through spontaneous ring closure. The activity of the derivatives was assessed using doxorubicin-sensitive and -resistant colon adenocarcinoma cell lines and normal human fibroblasts. Some derivatives possessed selective toxicity towards resistant cancer cells compared to doxorubicin-sensitive cancer cells and normal fibroblasts. Cytotoxic activity of the benzylidene derivatives and the corresponding Hammett–Brown substituent were correlated. Full article
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines 2022)
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24 pages, 5436 KB  
Review
KYNA Derivatives with Modified Skeleton; Hydroxyquinolines with Potential Neuroprotective Effect
by Bálint Lőrinczi and István Szatmári
Int. J. Mol. Sci. 2021, 22(21), 11935; https://doi.org/10.3390/ijms222111935 - 3 Nov 2021
Cited by 9 | Viewed by 3261
Abstract
Kynurenic acid (KYNA) is an endogenous neuroprotective agent of increasing importance. Several derivatives have already been synthesized, bearing an abundance of functional groups attached to the main skeleton in different positions. Several of these compounds have already been tested in biological evaluations, with [...] Read more.
Kynurenic acid (KYNA) is an endogenous neuroprotective agent of increasing importance. Several derivatives have already been synthesized, bearing an abundance of functional groups attached to the main skeleton in different positions. Several of these compounds have already been tested in biological evaluations, with several of them targeting the same receptors and biological effects as KYNA. However, these modified compounds build upon the unmodified KYNA skeleton leaving a possible route for the synthesis of new, potentially neuroprotective derivatives with heteroatom-containing ring systems. The aim of this review is to summarize the syntheses of KYNA derivatives with altered skeletons and to pinpoint an appealing transformation for future medicinal lead molecules. Full article
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines)
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