Synthesis of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones via Ugi–Zhu reaction and in vitro activity assays against human SARS-CoV-2 and in silico studies on its main proteins

Abstract

An Ugi-Zhu three-component reaction (UZ-3CR) coupled in one pot manner to a cascade process (N-acylation/aza Diels-Alder cycloaddition/decarboxylation/dehydration) was performed to synthesize a series of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones in 45 to 82% overall...

Hepatoprotective Activity, In Silico Analysis, and Molecular Docking Study of Verbascoside from Leucophyllum frutescens in Rats with Post-Necrotic Liver Damage

“…This is important because LE is generally a better parameter to compare the interaction of two or more molecules with a selected target. Despite the use of LE, in prior works, this parameter has been shown to correlate with experimental results [53]. A more negative value of LE indicates an improved interaction.…”

Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Ugi–Zhu Reaction and In Vitro–In Silico Studies against Breast Carcinoma

“…Synthesis 3.1.1. General Information, Instrumentation, Software, and Chemicals 1 H and 13 C nuclear magnetic resonance (NMR) spectra were acquired on a Bruker AMX Advance III spectrometer (500 MHz, Fällande, Uster, Switzerland). The solvent used for NMR experiments was deuterated chloroform (CDCl 3 ).…”

“…According to the GP, 3-Pyridinecarboxaldehyde (100.0 µL), 3-Picolylamine (107.0 µL), ytterbium(III) triflate (19.0 mg), N,N-diethyl-2-isocyano-3-phenylpropanamide (289.0 mg), and maleic anhydride (143.0 mg) were reacted together in toluene (1.0 mL) to afford 1g 2-benzyl-3-(piperidin-1-yl)-6-(pyridin-3-ylmethyl)-7-(pyridin-4-yl)-6,7-dihydro-5H-pyrrolo [3,4b]pyridin-5-one (1h) According to the GP, 4-Pyridinecarboxaldehyde (100.0 µL), 3-Picolylamine (106.0 µL), ytterbium(III) triflate (19.0 mg), 2-isocyano-3-phenyl-1-(piperidin-1-yl)propan-1-one (300.0 mg), and maleic anhydride (141.0 mg) were reacted together in toluene (1.0 mL) to afford 1h (25.0 mg, 20%) as a yellow oil; R f = (Hex-AcOEt = 1:1, v/v); FT-IR (ATR) ν max /cm −1 1694 (C = O); 1 H NMR (500 MHz, CDCl 3 ): δ 8.62-8.60 (m, 2H), 8.53 (dd, J = 4.8, 1.7 Hz, 1H), 8.42-8.40 (m, 1H), 7.84 (s, 1H), 7.56-7.53 (m, 1H), 7.23 (ddd, J = 7.8, 4.8, 0.9 Hz, 1H), 7.17-7.12 (m, 5H), 7.10-7.08 (m, 2H), 5.40 (d, J = 15.2 Hz, 1H), 5.18 (s, 1H), 4.23 (d, J = 13.9 Hz, 1H), 4.12 (d, J = 13.9 Hz, 1H), 3 According to the GP, 2-Pyridinecarboxaldehyde (100 µL), 3-Picolylamine (108 µL), ytterbium(III) triflate (19 mg), N,N-diethyl-2-isocyano-3-phenylpropanamide (291 mg), and maleic anhydride (144 mg) were reacted together in toluene (1.0 mL) to afford 1j (90 mg, 74%) as a yellow oil; R f = (Hex-AcOEt = 1:1, v/v); FT-IR (ATR) ν max /cm −1 1692 (C = O); 1 H NMR (500 MHz, CDCl 3 ): δ 8.60 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 8.47 (dd, J = 4.8, 1.7 Hz, 1H), 8.41 (dd, J = 2.3, 0.8 Hz, 1H), 7.88 (s, 1H), 7.61 (dddd, J = 7.7, 5.1, 2.7, 1.8 Hz, 2H), 7.23 (ddd, J = 7.6, 4.9, 1.2 Hz, 1H), 7.19 (ddd, J = 7.9, 4.8, 0.8 Hz, 1H), 7.14-7.11 (m, 5H), 7.03 (d, J = 7.8, 1.0 Hz, 1H), 5.47 (s, 1H), 5.22 (d, J = 15.1 Hz, 1H), 4.25 (d, J = 13.9 Hz, 1H), 4.23-4.17 (m, 2H), 2.97 (q, J = 7.1 Hz, 4H), 0.92 (t, J = 7.1 Hz, 6H) ppm; 13 C NMR (125 MHz, CDCl 3 ): δ 167. 5, 163.6, 158.4, 155.3, 149.9, 149.8, 148.9, 146.7, 139.4, 136.8, 136.3, 132.6, 129.5, 128…”

“…Supplementary Materials:The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ph16111562/s1, (1) workflow, (2) structures of compounds in vitro assayed, (3) spectra of all new compounds ( 1 H NMR,13 C NMR, HRMS and FT-IR, (4) in silico study details (docking data and molecular dynamics), and (5) supplementary references.…”

In Vitro and In Silico Studies of Bis-furyl-pyrrolo[3,4-b]pyridin-5-ones on Dengue Virus

“…In a previous work [19], we reported the synthesis of a series of six new bis-furyl-pyrrolo [3,4b]pyridin-5-ones, which exhibited moderate activity against human SARS-CoV-2. By evaluating the efficacy of these compounds in the Dengue replicon system and DENV4 infection, we aim to investigate their potential as antiviral agents against DENV.…”