Design, Practical Synthesis, and Biological Evaluation of Novel 6-(Pyrazolylmethyl)-4-quinoline-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors

Hu, Liming; Shu, Yan; Luo, Zaigang; Han, Xiao; Wang, Yujie; Wang, Zhanyang; Zeng, Cheng‐Chu

doi:10.3390/molecules170910652

Cited by 20 publications

(6 citation statements)

References 22 publications

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“…As far as we are aware, L1 represents only the second example of a bis(pyrazolyl)methyl that decorates an aniline; the first was Manzano's (2‐NH 2 C 6 H 4 )CHpz* 2 . The related compounds (2‐ or 4‐NH 2 C 6 H 4 )Cpz 3 and (4‐NH 2 C 6 H 4 )CH 2 pz are also known.…”

Section: Resultsmentioning

confidence: 99%

Supramolecular Assembly of Metal‐Organic Tubes Constructed from the Ditopic Heteroscorpionate Ligand (4‐NH2C6H4)CHpz2 (pz = Pyrazol‐1‐yl) and Silver(I)

et al. 2015

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The possibility of constructing tubular metal-organic structures with aid of weak hydrogen-bonding interactions between suitably designed metallacycles was explored. For this purpose, the new heteroditopic ligand (4-NH 2 C 6 H 4 )CHpz 2 (L1) was prepared in good (75 %) yield by a one-pot procedure starting from commercial 4-acetamidobenzaldehyde. The equimolar reactions between L1 and various silver(I) salts gave the intended 1:1 complexes in which the metallacycles were assembled into tubes. However, the exact nature of the assem- [a] Scheme 1. Some heteroditopic heteroscorpionate ligands (top) and a sampling of supramolecular isomers formed after metal coordination (bottom). Results and Discussion SynthesisThe new ligand (4-H 2 NC 6 H 4 )CHpz 2 (L1) was prepared by two different routes, as summarized in Scheme 2. Of the two pathways, Method A (Scheme 2, top) is preferred, because a 75 % yield can be obtained after a one-pot, two-step reaction sequence starting from commercial and inexpensive reagents. The yield of the CoCl 2 -catalyzed Peterson rearrangement [16] between the aldehyde and S(O)pz 2 was improved by 10-20 % by using an excess of S(O)pz 2 (relative to cases in which a 1:1 stoichiometric ratio of reagents was used). It is also noted that the rate of hydrolysis of the intermediate, {4-[CH 3 C(O)NH]C 6 H 4 }-CHpz 2 , is greatly enhanced in aqueous solution with respect to in solvent mixtures (THF/water or methanol/water). That is, after monitoring of the amide deprotection reaction by TLC, the rate of hydrolysis was observed to increase with water content of the solvent mixture. The deprotection reaction did not proceed to any appreciable extent when mixtures of NaOH (or KOH) and the intermediate were heated at reflux in dry MeOH over the course of a day, but the reaction was complete within hours when only water was used as a solvent. The ligand has significant solubility in water and in basic solution; this slightly complicates its extraction into organic solvents. That is, yields can be artificially low if care is not taken to ensure complete extraction by using numerous aliquots of organic solvent (ethyl acetate was particularly effective) and by checking the aqueous layer for product by TLC.

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Section: Resultsmentioning

confidence: 99%

Supramolecular Assembly of Metal‐Organic Tubes Constructed from the Ditopic Heteroscorpionate Ligand (4‐NH2C6H4)CHpz2 (pz = Pyrazol‐1‐yl) and Silver(I)

et al. 2015

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“…The most active compound 21a exhibited potential activity against wt HIV‐1 and HIV‐1 mutant virus A17 with EC 50 values of 3.17 and 17.88 µM, respectively, but it was far less potent than elvitegravir (EC 50 : 0.00021 and 0.0010 µM). For 4‐quinolone‐pyrazole hybrids 22 , the esters 22a,b and acids 22c,d (IC 50 : >100 µM) were inactive against HIV‐1 IN, while the phenol‐containing hybrids 22e,f (IC 50 : 21.16 and 2.60 µM) showed considerable activity . The 4‐quinolone‐metronidazole hybrids 23 (Figure ) displayed promising antifungal activities against C. tropicalis , C. albicans and G. intestinals , but they were devoid of activity against HIV‐1 IIIB and HIV‐2 ROD (EC 50 : >19.22 µM) …”

Section: ‐Quinolone Derivativesmentioning

confidence: 99%

Quinolone derivatives: Potential anti‐HIV agent—development and application

Wang

Shi

2019

Archiv der Pharmazie

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“…В ря-ду N-алкілзаміщених 4-оксохінолін-3-карбонових кислот виявлені сполуки, що проявляють анти-мікробну активність [1][2][3][4][5][6], антимікобактеріаль-ну дію [7][8][9], а також є інгібіторами інтегрази ВІЛ [10] та вірусу гепатиту С [11].…”

Section: Issn 2308-8303unclassified

A convenient approach to the synthesis of substituted 2-(methylamino)quinoline-3-carboxamides

Muzychka¹,

Смолий²,

Biletskiy³

et al. 2015

J. org. pharm. chem.

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Design, Practical Synthesis, and Biological Evaluation of Novel 6-(Pyrazolylmethyl)-4-quinoline-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors

Cited by 20 publications

References 22 publications

Supramolecular Assembly of Metal‐Organic Tubes Constructed from the Ditopic Heteroscorpionate Ligand (4‐NH2C6H4)CHpz2 (pz = Pyrazol‐1‐yl) and Silver(I)

Supramolecular Assembly of Metal‐Organic Tubes Constructed from the Ditopic Heteroscorpionate Ligand (4‐NH2C6H4)CHpz2 (pz = Pyrazol‐1‐yl) and Silver(I)

Quinolone derivatives: Potential anti‐HIV agent—development and application

A convenient approach to the synthesis of substituted 2-(methylamino)quinoline-3-carboxamides

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