Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors

Jia, Haiyong; Bai, Fuxiang; Liu, Na; Liang, Xiaohong; Zhan, Peng; Ma, Chao; Jiang, Xuemei; Liu, Xinyong

doi:10.1016/j.ejmech.2016.07.048

Cited by 33 publications

(12 citation statements)

References 21 publications

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“…Jia et al identified a series of novel pyrazole derivatives as non-nucleoside HBV inhibitors via bioisosterism and pharmacophore hybrid strategy. In particular, compound 424 displayed the most potent activity against the secretion of HBsAg and HBeAg with IC 50 of 24.33 µM and 2.22 µM, respectively [ 322 ]. A series of pyrrolopyrazole derivatives were synthesized by Liu et al and evaluated for their anti-viral activity against HIV-1.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

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Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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“…In combination with their favorable drug-like properties, privileged structures or scaffolds are widely used in rational drug design to find new lead compounds or drug candidates [1,2,3]. Pyrazole derivatives represent one of the most active classes of compounds that possess a wide spectrum of biological activities, including antibacterial and antifungal [4,5], antitumor [6,7], anti-inflammatory and analgesic [8,9], antitubercular [10], antiviral [11,12], anti-Alzheimer’s [13,14], α-glucosidase inhibitory [15], anti-diabetic [16], antileishmanial [17,18], anti-malarial [19], radioimaging [20], acaricidal and insecticidal [21,22] activities. As a privileged scaffold, pyrazole has been recently widely used in the design of anticancer agents for a multiple of tumor targets [23].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

et al. 2019

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To find novel antitumor agents, a series of 1H-benzofuro[3,2-c]pyrazole derivatives 4a-e were designed and synthesized. The treatment of 6-methoxybenzofuran-3(2H)-one 3 with LiHMDS in anhydrous tetrahydrofuran (THF) followed by reaction with 3-substitued phenyl isothiocyanate gave the thioamide intermediates, which underwent condensation with hydrazine monohydrate in dioxane/EtOH (1:1) to provide the benzofuropyrazole derivatives 4a–e as well as the unexpected pyrazole derivatives 5a–e. In tumor cell growth inhibitory assay, all the benzofuropyrazole derivatives were not active against the breast tumor MCF-7 cell, only 4a was highly active and more potent than ABT-751 against the leukemia K562 (GI50 = 0.26 μM) and lung tumor A549 cells (GI50 = 0.19 μM), while other benzofuropyrazoles showed very weak inhibitory activity. In contrast, the pyrazoles 5a-e were in general more potent than the benzofuropyrazoles 4a–e. Compound 5a exhibited a similar tendency to that of 4a with high potency against K562 and A549 cells but weak effects on MCF-7 cell. Both pyrazoles 5b and 5e exhibited high inhibitory activities against K562, MCF-7 and A549 cells. The most active compound 5b was much more potent than ABT-751 against K562 and A549 cells with GI50 values of 0.021 and 0.69 μM, respectively. Moreover, 5b was identified as a novel tubulin polymerization inhibitor with an IC50 of 7.30 μM.

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“…The target compounds were evaluated for their cytotoxicity, inhibitory effect on HBV DNA replication, and HBsAg and HBeAg secretion in HepG2.2.15 cells (human HBV transgenic HCC cells) via Cell Counting Kit‐8 (CCK‐8), PCR, and standard ELISA method, respectively. The biological results were represented as inhibition percentages, IC 50 values, CC 50 values, and selectivity index (SI) values (determined as the CC 50 /IC 50 values) (Jia et al., , ).…”

Section: Resultsmentioning

confidence: 99%

“…HepG2.2.15 cells were cultured in triplicate of 96‐well tissue culture plates with five different doses of tested compounds (Jia et al., ). The culture medium was replaced with a fresh one on day 4 during the 8‐day experiment.…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non‐nucleoside hepatitis B virus inhibitors by exploring the solvent‐exposed region

Jia

Guo

et al. 2020

Chem Biol Drug Des

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In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most Haiyong Jia is the co-first author. 568 | YU et al. F I G U R E 1 The structures of six nucleoside/nucleotide reverse transcriptase inhibitors approved by US Food and Drug Administration for hepatitis B virus therapy [Colour figure can be viewed at wileyonlinelibrary.com] potent activity against HBV DNA replication (IC 50 = 0.35 ± 0.04 μM). The preliminary structure-activity relationships of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design. K E Y W O R D S capsid, HAP, HBV, protein-solvent interface, sulfonamide, triazoles Yellow solid, yield: 61%, mp: 79-83°C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.78 (d, J = 3.1 Hz, 1H), 7.76 (s, 1H), 7.46 (d, J = 2.9 Hz, 1H), 7.39-7.25 (m, 2H), 7.02 (td, J = 8.3, 2.3 Hz, 1H), 6.13 (s, 1H), 5.93 (dd, J = 15.4, 7.7 Hz, 1H), 5.82 (dd, J = 15.4, 7.5 Hz, 1H), 4.93 (t, J = 6.5 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H), 2.60 (s, 1H), 1.99-1.84 (m, 2H), 1.63-1.28 (m, 4H), 1.15 (t, J = 7.1 Hz, 3H), 0.88 (t, J = 7.1 Hz, 3H); EI-MS: 577.5 [M + H] + .Ethyl 4-Yellow solid, yield: 47%, mp: 85-89°C; 1H NMR (400 MHz, CDCl 3 ) δ: 7.93 (s, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 3.1 Hz, 1H), 7.30 (ddd, J = 15.0, 7.8, 5.2 Hz, 3H), 7.20

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Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors

Cited by 33 publications

References 21 publications

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non‐nucleoside hepatitis B virus inhibitors by exploring the solvent‐exposed region

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