Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors.

doi:10.1021/jm2015952

Paper

DOI: 10.1021/jm2015952

Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors.

Published Mar 26, 2012 · Bo Chao, Xiankun Tong, Wei Tang

Journal of medicinal chemistry

Q1 SJR score

Citations

Influential Citations

Full textSemantic Scholar

Abstract

The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.

In Vitro Study

Study Snapshot

2,4-diaminoquinazoline derivatives show high dengue virus inhibitory activity and excellent pharmacokinetic profiles, with 4o showing the highest antiviral potency and pharmacokinetic profile.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Full text analysis coming soon...

References

DOI: 10.1021/jm200903z

Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines.

UNC0646 and UNC0631 are novel G9a inhibitors with excellent cellular activity and low toxicity, enhancing their potential as cancer treatments.

2011·131citations·Feng Liu et al.·Journal of medicinal chemistry

Journal of medicinal chemistry

DOI: 10.1016/j.bmc.2011.05.015

Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture.

-ketoamides show potential as inhibitors of Dengue virus protease, with antiviral activity confirmed in a cell-culture model of virus replication.

2011·116citations·Christian Steuer et al.·Bioorganic & medicinal chemistry

Bioorganic & medicinal chemistry

DOI: 10.1016/j.antiviral.2010.12.006

Anthracene-based inhibitors of dengue virus NS2B-NS3 protease.

Anthracene-based inhibitors of dengue virus NS2B-NS3 protease show promising potential as a new antiviral drug target for dengue-related illnesses.

2011·72citations·Suzanne M. Tomlinson et al.·Antiviral research

Antiviral research

DOI: 10.1016/j.antiviral.2010.09.002

Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein.

Chondroitin sulphate E (CSE) shows antiviral activity as an entry inhibitor targeting dengue virus envelope protein, suggesting a specific carbohydrate structure is necessary for binding.

2010·100citations·Daisuke Kato et al.·Antiviral research

Antiviral research

DOI: 10.1021/jm100593s

Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses.

The novel 7-deaza-6-methyl-9--D-ribofuranosylpurine analogue effectively inhibits poliovirus and dengue virus replication, with selectivity against poliovirus and cytotoxic effects to HeLa cells.

2010·51citations·Runzhi Wu et al.·Journal of medicinal chemistry

Journal of medicinal chemistry

DOI: 10.1128/AAC.00855-10

Novel Dengue Virus-Specific NS2B/NS3 Protease Inhibitor, BP2109, Discovered by a High-Throughput Screening Assay

BP2109 is a potent and selective inhibitor of dengue virus NS2B/NS3 protease, potentially offering a new treatment option for dengue fever.

2010·105citations·Chi-Chen Yang et al.·Antimicrobial Agents and Chemotherapy

Antimicrobial Agents and Chemotherapy

DOI: 10.1128/AAC.00686-10

A Derivate of the Antibiotic Doxorubicin Is a Selective Inhibitor of Dengue and Yellow Fever Virus Replication In Vitro

SA-17, a doxorubicin derivate, selectively inhibits dengue and yellow fever virus replication in vitro, with a selectivity index value of 100, but shows inactivity against various enveloped and nonenveloped viruses.

2010·78citations·Suzanne J. F. Kaptein et al.·Antimicrobial Agents and Chemotherapy

Antimicrobial Agents and Chemotherapy

DOI: 10.1021/jm100478y

Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.

The study developed a new class of G9a inhibitors, revealing their excellent selectivity and potential for cancer treatment.

2010·189citations·Feng Liu et al.·Journal of medicinal chemistry

Journal of medicinal chemistry

DOI: 10.1016/j.antiviral.2010.05.003

Biochemical characterization of the inhibition of the dengue virus RNA polymerase by beta-d-2'-ethynyl-7-deaza-adenosine triphosphate.

Beta-d-2′-ethynyl-7-deaza-adenosine triphosphate effectively inhibits dengue virus RNA polymerase, providing a promising scaffold for developing inhibitors of dengue virus polymerase.

2010·42citations·Derek Latour et al.·Antiviral research

Antiviral research

Citations

DOI: 10.3390/molecules29102232

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview

N-heterocycles show promising antiviral activity and can stimulate the host's immune system, potentially leading to effective antiviral drugs with minimal side effects.

2024·7citations·Gulraiz Ahmad et al.·Molecules

Molecules

DOI: 10.3390/v15112194

Identification of 2,4-Diaminoquinazoline Derivative as a Potential Small-Molecule Inhibitor against Chikungunya and Ross River Viruses

DCR 137, a quinazoline derivative, shows potential as a pan-alphavirus inhibitor by effectively inhibiting CHIKV and Ross River virus replication.

2023·2citations·Amrita Saha et al.·Viruses

Viruses

DOI: 10.3390/molecules26237338

Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors

4-anilinoquinolines show potential as dengue virus inhibitors and Venezuelan Equine Encephalitis virus inhibitors, with limited toxicity and potential for further refinement into clinical compounds against these emerging viral threats.

2021·4citations·P. Huang et al.·Molecules

Molecules

DOI: 10.1016/j.bmcl.2021.128407

Evaluation and identification of 4-anilinoquin(az)olines as potent inhibitors of both dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV).

Three potent 4-anilinoquinolines and 4-anilinoquinazolines show potential as novel treatments for dengue and Venezuelan equine encephalitis viruses, with nearly no toxicity.

2021·9citations·Sirle Saul et al.·Bioorganic & medicinal chemistry letters

Bioorganic & medicinal chemistry letters

DOI: 10.1016/j.bmcl.2020.127284

Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines.

Novel 6-substituted bromine and iodine derivatives show potent inhibitory activity against dengue virus with limited toxicity, offering a promising series for further development.

2020·23citations·Sirle Saul et al.·Bioorganic & medicinal chemistry letters

Bioorganic & medicinal chemistry letters

DOI: 10.1021/acs.orglett.9b04395

Silver-Catalyzed Annulation of Arynes with Nitriles for Synthesis of Structurally Diverse Quinazolines.

Silver-catalyzed annulation of arynes with nitriles efficiently generates structurally diverse quinazolines with excellent regioselectivity.

2019·18citations·S. Ghorai et al.·Organic letters

Organic letters

DOI: 10.1021/acs.jmedchem.9b00698

Design, Synthesis, and Biological Evaluation of Substituted 4,6-Dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione Analogues as Potent NS4B Inhibitors for the Treatment of Dengue Virus Infection.

Substituted 4,6-dihydrospiro[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione analogues show potential as potent NS4B inhibitors for treating

2019·25citations·Jimin Xu et al.·Journal of medicinal chemistry

Journal of medicinal chemistry

DOI: 10.1016/j.ejmech.2018.01.008

Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors.

Phtalazinone derivatives, such as 14l, show potential as potent dengue virus inhibitors with high selectivity and acceptable pharmacokinetic profiles.

2018·17citations·Dong Lu et al.·European journal of medicinal chemistry

European journal of medicinal chemistry