Facile synthesis of highly functionalized novel pyrazolopyridones using oxoketene dithioacetal and their anti-HIV activity

Savant, Mahesh M.; Ladva, Kartik D.; Pandit, Archna B.

doi:10.1080/00397911.2018.1458239

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…The intermediate 4 was further diversified to rapidly generate fused heteroaromatic cores by reacting it with the corresponding amines ( 5 , 6 and 7 ) under thermal conditions [ 46 ] to yield ZW-1841, ZW-1842, and ZW-1843. Pyrazolopyridone chemotype ZW-1847 was obtained via a three-step process starting from the intermediate 3 [ 47 ]. First, compound 3 was added to CS 2 in base-mediated fashion followed by a methylation to yield oxoketene dithioacetal intermediate 8 .…”

Section: Methodsmentioning

confidence: 99%

Discovery of New Small Molecule Hits as Hepatitis B Virus Capsid Assembly Modulators: Structure and Pharmacophore-Based Approaches

Senaweera

Zhang

et al. 2021

Viruses

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Hepatitis B virus (HBV) capsid assembly modulators (CpAMs) have shown promise as potent anti-HBV agents in both preclinical and clinical studies. Herein, we report our efforts in identifying novel CpAM hits via a structure-based virtual screening against a small molecule protein-protein interaction (PPI) library, and pharmacophore-guided compound design and synthesis. Curated compounds were first assessed in a thermal shift assay (TSA), and the TSA hits were further evaluated in an antiviral assay. These efforts led to the discovery of two structurally distinct scaffolds, ZW-1841 and ZW-1847, as novel HBV CpAM hits, both inhibiting HBV in single-digit µM concentrations without cytotoxicity at 100 µM. In ADME assays, both hits displayed extraordinary plasma and microsomal stability. Molecular modeling suggests that these hits bind to the Cp dimer interfaces in a mode well aligned with known CpAMs.

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Section: Methodsmentioning

confidence: 99%

Discovery of New Small Molecule Hits as Hepatitis B Virus Capsid Assembly Modulators: Structure and Pharmacophore-Based Approaches

Senaweera

Zhang

et al. 2021

Viruses

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“…Fused-pyrazoles have been found to exhibit several biological properties like anti-inflammatory [ 10 ], anti-viral [ 11 ], anti-tumor [ 12 ], anti-microbial [ 13 ], and antiprotozoal [ 14 ]. In addition, many fused-pyrazoles have shown significant anti-human immunodeficiency virus (HIV) properties [ 15 ]. The anti-HIV activity of 1H-pyrazolo[3,4-b]pyridine-3-yl compounds is associated with inhibition of reverse transcriptase [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, many fused-pyrazoles have shown significant anti-human immunodeficiency virus (HIV) properties [ 15 ]. The anti-HIV activity of 1H-pyrazolo[3,4-b]pyridine-3-yl compounds is associated with inhibition of reverse transcriptase [ 15 ]. Another series of pyrazoles has been reported to exhibit anti-HIV property against both HIV-1 (IIIB) and HIV-2 (ROD) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…The anti-HIV activity of 1H-pyrazolo[3,4-b]pyridine-3-yl compounds is associated with inhibition of reverse transcriptase [ 15 ]. Another series of pyrazoles has been reported to exhibit anti-HIV property against both HIV-1 (IIIB) and HIV-2 (ROD) [ 15 ]. The present study evaluated pyrazolo[4,3-c]pyridine-4-one (PP-4-one) derivative ( Figure 1 ) an anti-proliferative agent against glioma cells and investigated the associated mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Glioma Cell Growth and Apoptosis Induction through Targeting Wnt10B Expression by Pyrazolo[4,3-c]pyridine-4-one

Zhu

Peng

et al. 2020

Med Sci Monit

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Background Gliomas are commonly diagnosed tumors in the central nervous system that have an elevated mortality rate. The present study evaluated pyrazolo[4,3-c]pyridine-4-one (PP-4-one) as an anti-proliferative agent against glioma cells and investigated the associated mechanism. Material/Methods The changes in cell growth were analyzed by Cell Counting Kit-8 (CCK-8) and apoptosis by flow cytometry using Annexin V-FITC staining kit. The FACSCalibur flow cytometer was used for analysis of DNA content and western blotting for protein expression. Results The PP-4-one treatment suppressed viability of U251, C6, and U87 cells significantly at a concentration of 0.25 μM. At a concentration of 16 μM, PP-4-one treatment for 72 hours suppressed viability of U251, C6, and U87 cells to 24%, 21%, and 20%, respectively. Treatment with PP-4-one suppressed cyclic 3′,5′-adenosine monophosphate (cAMP) levels in U251 and C6 cells significantly ( P <0.05) depending on the concentration. The apoptotic cells were increased significantly ( P <0.05) by PP-4-one treatment in U251 and C6 cell cultures. A considerable enhancement in the proportion of U251 and C6 cells in the G0/G1 phase was recorded on incubation with PP-4-one. Treatment of U251 and C6 cells with PP-4-one markedly enhanced p21 expression relative to the control. The B-cell lymphoma (Bcl-2) level in PP-4-one treated U251 and C6 cells was markedly lower relative to the control cells. The Bax, caspase-3, and caspase-9 levels were elevated markedly by PP-4-one treatment in U251 and C6 cells. Conclusions This study demonstrated that PP-4-one has anti-proliferative potential for glioma cells via targeting cAMP and Bcl-2 levels. It also promoted glioma cell apoptosis through caspase activation and arrest of the cell cycle. Thus, PP-4-one may be used to develop drug candidates for the glioma treatment.

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Bicyclic 5-6 Systems: Three Heteroatoms 2:1

Sápi

Gérard

2022

Comprehensive Heterocyclic Chemistry IV

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Facile synthesis of highly functionalized novel pyrazolopyridones using oxoketene dithioacetal and their anti-HIV activity

Cited by 7 publications

References 33 publications

Discovery of New Small Molecule Hits as Hepatitis B Virus Capsid Assembly Modulators: Structure and Pharmacophore-Based Approaches

Discovery of New Small Molecule Hits as Hepatitis B Virus Capsid Assembly Modulators: Structure and Pharmacophore-Based Approaches

Inhibition of Glioma Cell Growth and Apoptosis Induction through Targeting Wnt10B Expression by Pyrazolo[4,3-c]pyridine-4-one

Bicyclic 5-6 Systems: Three Heteroatoms 2:1

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