Discovery and optimizing polycyclic pyridone compounds as anti-HBV agents

Wei, Fenju; Kang, Dongwei; Cherukupalli, Srinivasulu; Zalloum, Waleed A.; Zhang, Tao; Liu, Xinyong; Zhan, Peng

doi:10.1080/13543776.2020.1801641

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…[8][9][10] Pyridine derivatives, one of the important N-heterocycles, exhibit a wide variety of essential pharmacological activities, including antimicrobial, [11] antiviral, [12] antifungal and antimycobacterial [13] as well as anticancer [14] activities. Pyridinones have also attracted significant interest from researchers due to their crucial biological activities, such as antibacterial, [15] anti-inflammatory, [16] anti-hepatitis B virus, [17] SARS-CoV-2 main protease inhibitor [18] and anticancer. [19] Several review articles have focused on this class of compounds because of their medicinal applications.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Novel 1‐((1‐Phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one Derivatives

Keskin

2023

ChemistrySelect

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The synthesis of a new class of compounds, namely 1‐((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one derivatives starting from 2‐hydroxynicotinic acid was reported. Initially, the carboxylic acid functionality connected to the pyridinone ring was converted to either the ester, amide or aldehyde functionality to obtain the precursor for the propargylation step. The incorporation of a propargyl group into the nitrogen atom of pyridinones was achieved in the presence of K2CO3 as a base. Different organic azides were also synthesized starting from the corresponding aniline derivatives. To obtain target molecules, the facile click cycloaddition reactions of alkynes with aryl azide derivatives in the presence of copper(I) catalyst were applied. Using this protocol, novel 1‐((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one derivatives with different substitution patterns were prepared in good to excellent yields under the mild reaction conditions. The structures of the compounds were confirmed by 1D and 2D NMR, FTIR, and HRMS analysis data. Overall, this protocol offers a straightforward method for synthesizing these novel compounds.

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Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Novel 1‐((1‐Phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one Derivatives

Keskin

2023

ChemistrySelect

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“…Recently, pyridinone derivatives have attracted attention due to their versatile pharmaceutical, agricultural, and industrial applications [14]. Pyridinone-containing compounds show a broad spectrum of pharmacological properties such as SARS-CoV-2 main protease inhibitor [15], antihepatitis B virus [16], antitumor [17], antiproliferative [18], antibacterial [19], antiinflammatory [20] and analgesic [21] activities. The pyridine scaffold has become a hot point in medicinal chemistry, and an increasing number of FDA-approved drugs have reinforced its significance.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new 2‐pyridinone and thiazole derivatives containing coumarin moiety

Al‐Harbi,

Emam,

Abbas

2023

Journal of Heterocyclic Chem

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Coumarin has shown considerable therapeutic potency because of its versatile biological prosperities. Also, pyridines have been adopted in medicinal chemistry as potent ring. Moreover, several investigations reported the potency of thiazole‐containing compounds. So, during this research, new functionalized 2‐pyridinone and thiazole derivatives bearing coumarin moiety were aimed to synthesize. Many trials to obtain the 6‐amino‐2‐oxo‐pyridine‐3,5‐dicarbonitriles through the condensation of cyanoacetohydrazone of 3‐acetyl coumarin with 2‐(arylidene)malononitriles were carried out using different reaction conditions. In all cases, the reaction gave none of the corresponding 2‐pyridinone derivatives except the reaction with 2‐(benzylidene)‐malononitrile afforded product in few yield. Moreover, the reaction of another cyanoacetanilide with the 2‐(arylidene)‐malononitrile afforded the unexpected arylidene derivatives rather than the expected pyridin‐2‐one derivatives. Finally, new thiazoles bearing coumarin moiety were synthesized using 3‐acetylcoumarin N‐(2,4‐dimethoxyphenyl)‐thiosemicarbazone. Cyclization of thiosemicarbazone derivative with ethyl 2‐chloroacetate, chloroacetone or phenacyl bromide afforded in high yields the corresponding derivatives of thiazolidin‐4‐one, 4‐methylthiazole or 4‐phenylthiazole, respectively.

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“…Hit-to-lead (H2L) is employed to optimize the structure of the compounds, which has been increasingly studied in medicinal chemistry. It has been used against hepatitis B virus (HBV) polycyclic pyridone drugs [ 35 ]. In research on antimalarial drugs, two potential drugs were designed via the H 2 L method, and the obtained compound activities were verified [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Computer-Aided and AILDE Approaches to Design Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Shi¹,

Gao²,

Wang³

et al. 2022

IJMS

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4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a pivotal enzyme in tocopherol and plastoquinone synthesis and a potential target for novel herbicides. Thirty-five pyridine derivatives were selected to establish a Topomer comparative molecular field analysis (Topomer CoMFA) model to obtain correlation information between HPPD inhibitory activity and the molecular structure. A credible and predictive Topomer CoMFA model was established by “split in two R-groups” cutting methods and fragment combinations (q2 = 0.703, r2 = 0.957, ONC = 6). The established model was used to screen out more active compounds and was optimized through the auto in silico ligand directing evolution (AILDE) platform to obtain potential HPPD inhibitors. Twenty-two new compounds with theoretically good HPPD inhibition were obtained by combining the high-activity contribution substituents in the existing molecules with the R-group search via Topomer search. Molecular docking results revealed that most of the 22 fresh compounds could form stable π-π interactions. The absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction and drug-like properties made 9 compounds potential HPPD inhibitors. Molecular dynamics simulation indicated that Compounds Y12 and Y14 showed good root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values and stability. According to the AILDE online verification, 5 new compounds with potential HPPD inhibition were discovered as HPPD inhibitor candidates. This study provides beneficial insights for subsequent HPPD inhibitor design.

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Discovery and optimizing polycyclic pyridone compounds as anti-HBV agents

Cited by 9 publications

References 39 publications

Design and Synthesis of Novel 1‐((1‐Phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one Derivatives

Design and Synthesis of Novel 1‐((1‐Phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)pyridin‐2(1H)‐one Derivatives

Synthesis of new 2‐pyridinone and thiazole derivatives containing coumarin moiety

Computer-Aided and AILDE Approaches to Design Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

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