ArticleJournal of medicinal chemistry2014
Development of (E)-2-((1,4-dimethylpiperazin-2-ylidene)amino)-5-nitro-N-phenylbenzamide, ML336: Novel 2-amidinophenylbenzamides as potent inhibitors of venezuelan equine encephalitis virus.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- Restructuring Antiviral Quinazolinone Frameworks to Derive and Optimize Inhibitors of Chikungunya Virus.ACS medicinal chemistry letters · 2025Article
- Article
- Broad spectrum antiviral BDGR-164 provides protection against lethal neurotropic alphavirus infection in mice.Antiviral research · 2025Article
- QSAR, molecular docking, molecular dynamics and DFT-based design of novel Quinoline-2-yl (piperazin-1-yl) inhibitors of hepatitis C virus.NAM journal · 2025Article
- TRIM32 inhibits Venezuelan equine encephalitis virus infection by targeting a late step in viral entry.PLoS pathogens · 2024Article
- TRIM32 inhibits Venezuelan Equine Encephalitis Virus Infection by targeting a late step in viral entry.bioRxiv : the preprint server for biology · 2024Article
- Mannich-Type Condensation and Domino Quinazolinone-Amidine Rearrangement Affords Ring-Fused Mackinazolinones with Anti-Amoebic Activity.Advanced synthesis & catalysis · 2023Article
- In Silico Screening of Inhibitors of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease.Viruses · 2023Article
- Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models.Science translational medicine · 2023Article
- Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses.Viruses · 2023Review
- Dihydropyrazinoquinazolinones via SThe Journal of organic chemistry · 2022Article
- Piperazinobenzodiazepinones: New Encephalitic Alphavirus Inhibitors via Ring Expansion of 2-Dichloromethylquinazolinones.ACS medicinal chemistry letters · 2022Article
- Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus.European journal of medicinal chemistry · 2022Article
- Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents.Frontiers in chemistry · 2022Article
- Diastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric (Organic letters · 2021Article
- Classification models and SAR analysis on CysLT1 receptor antagonists using machine learning algorithms.Molecular diversity · 2021Article
- Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.Journal of medicinal chemistry · 2021Article
- Construction ofAdvanced synthesis & catalysis · 2021Article
- Emergence and Magnitude of ML336 Resistance in Venezuelan Equine Encephalitis Virus Depend on the Microenvironment.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Venezuelan equine encephalitis virus (VEEV) is an emerging pathogenic alphavirus that can cause significant disease in humans. Given the absence of therapeutic options available and the significance of VEEV as a weaponized agent, an optimization effort was initiated around a quinazolinone screening hit 1 with promising cellular antiviral activity (EC50 = 0.8 μM), limited cytotoxic liability (CC50 > 50 μM), and modest in vitro efficacy in reducing viral progeny (63-fold at 5 μM). Scaffold optimization revealed a novel rearrangement affording amidines, specifically compound 45, which was found to potently inhibit several VEEV strains in the low nanomolar range without cytotoxicity (EC50 = 0.02-0.04 μM, CC50 > 50 μM) while limiting in vitro viral replication (EC90 = 0.17 μM). Brain exposure was observed in mice with 45. Significant protection was observed in VEEV-infected mice at 5 mg kg(-1) day(-1) and viral replication appeared to be inhibited through interference of viral nonstructural proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.