Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities

Docking, Synthesis and Biological Evaluation of Novel Diketoquinoline Analogues as HIV-1 Integrase Inhibitor

“…MS spectra of the synthesized compounds were recorded on Shimadzu QP-5050 spectrophotometer. 1 H NMR spectra were acquired on a Varian-300 (300 MHz NMR ) spectrophotometer using CDCl 3 and DMSOd 6 as solvent. The infrared spectra were obtained using a Perkin Elmer Spectrum ES Version 10.5.3 Fourier-transform infrared spectrometer.…”

“…232-34 °C. 1 Methyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(4-methoxybenzoyl)piperazin-1-yl)quinoline-3carboxylate: A solution of methyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)quinoline-3-carboxylate 2g (5.80 mmol) in N,N-dimethylformamide (20 mL), 4methoxybenzoic acid (0.88 g, 5.80 mmol) and DIPEA (2.26 mL, 17.40 mmol) were added and stirred at room temperature for 20 min, HATU (3.30 g, 8.70 mmol) was added and stirred at room temperature for 6 h. TLC shows completion of starting material. The reaction mixture was quenched with water, extracted with ethyl acetate, the combined organic layer was dried over sodium sulfate and concentrated under reduced pressure, the obtained crude product was purified by column chromatography using silica gel (100-200 mesh) and 5 % methanol in dichloromethane as eluent, desired organic fractions were distilled under reduced pressure to get methyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-methoxybenzoyl)piperazin-1-yl)quinoline-3-carboxylate.…”

“…Whereas structural studies of integrase reveal a single binding site for Mg 2+ , the number of metal ions present and required in the active site during the process remains controversial. A great number of HIV-1 integrase inhibitors with metal binding properties have been described and numerous reviews have been published [1][2][3][4].…”

“…In the present study, structures were docked in integrase pocket. In this context, we synthesized new diketoquinoline derivatives (1)(2)(3)(4)(5)(6)(7) by the replacement of various substituent's present on elvitegravir. All these compounds were evaluated for their antiintegrase activity.…”

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

“…All N ‐fluorobenzyl 4‐quinolone derivatives 24b–d (inhibition rate: <10% at 100 µM) had a significant negative effect on inhibition of HIV IN in contrast to the corresponding unsubstituted 24a (inhibition rate: 70% at 100 µM), indicating that fluorobenzyl group in compounds might lead to unfavorable physicochemical properties and poor anti‐HIV‐1 activity …”