☆ 4.7 Article

Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives as a New Class of Potent Dengue Virus Inhibitors

JOURNAL OF MEDICINAL CHEMISTRY (2012)

期刊

JOURNAL OF MEDICINAL CHEMISTRY

卷 55, 期 7, 页码 3135-3143

出版社

AMER CHEMICAL SOC

DOI: 10.1021/jm2015952

关键词

-

类别

Chemistry, Medicinal

资金

National Science Fair Committee of China [NSFC 81102477]
State Key Laboratory of Drug Research [SIMM1004KF-18]
DENFRAME of the European Union (EC) [517711]

向作者/读者索取更多资源

Protocol

Reagent

摘要

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 (EC50 = 0.15 mu M). 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 (EC50 = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.

作者

我是这篇论文的作者

点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7

评分不足

次要评分

新颖性

-

重要性

-

科学严谨性

-

评价这篇论文

推荐

Article Chemistry, Medicinal

Discovery of 2,4-pyrimidinediamine derivatives as potent dual inhibitors of ALK and HDAC

Tao Pan, Yanrong Dan, Dafeng Guo, Junhao Jiang, Dongzhi Ran, Lin Zhang, Binghua Tian, Jianyong Yuan, Yu Yu, Zongjie Gan

Summary: The newly designed compound 10f showed potent inhibitory activity against both ALK and HDAC, effective against resistant mutants and exhibiting significant anti-proliferative effects on cancer cells at low concentrations.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Discovery of non-nucleoside oxindole derivatives as potent inhibitors against dengue RNA-dependent RNA polymerase

Venkatanarayana Chowdary Maddipati, Lovika Mittal, Jaskaran Kaur, Yogita Rawat, Chandra Prakash Koraboina, Sankar Bhattacharyya, Shailendra Asthana, Rambabu Gundla

Summary: A series of thiazole linked Oxindole-5-Sulfonamide (OSA) derivatives were designed and synthesized as inhibitors of Dengue virus RNA-dependent RNA polymerase (RdRp) activity. The lead compound was identified as OSA-15, and analogues were further developed. The compounds OSA-15-17 and OSA-15-17-DM showed improved efficacy and no detectable cytotoxicity, with OSA-15-17-DM exhibiting the highest potency.

BIOORGANIC CHEMISTRY (2023)

添加到收藏夹

Article Chemistry, Medicinal

Discovery and Optimization of Quinoline Analogues as Novel Potent Antivirals against Enterovirus D68

Xiaoyuan Li, Yuexiang Li, Shiyong Fan, Ruiyuan Cao, Xiaojia Li, Xiaomeng He, Wei Li, Longfa Xu, Tong Cheng, Honglin Li, Wu Zhong

Summary: A series of novel quinoline analogues targeting VP1 were identified as potent anti-EV-D68 agents through virtual screening and rational design. Compound 19 exhibited strong antiviral activity against various EV-D68 strains and inhibited viral replication. Mechanistic studies indicated that these anti-EV-D68 agents mainly work by interacting with VP1.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Plant Sciences

Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents

Enjing Cui, Shihu Qian, Jiaming Li, Xueyang Jiang, Hongwei Wang, Shuaishuai Du, Le Du

Summary: In this study, 26 derivatives of Coixol were designed and synthesized to discover new anti-inflammatory agents. The derivatives containing furan or nitrofuran moieties exhibited stronger anti-inflammatory activity than Coixol and celecoxib, as evidenced by the reduced expression of iNOS, TNF-α, IL-6, and IL-1β. Mechanistic investigations revealed that the inhibition of the NF-κB signaling pathway contributed to the anti-inflammatory effects of 9c and 9j. In vivo studies confirmed their anti-inflammatory activity in a xylene-induced mice auricles edema model.

JOURNAL OF NATURAL PRODUCTS (2023)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of C-5 Pyrazole-Substituted Pyrrolopyridine Derivatives as Potent and Selective Inhibitors for Janus Kinase 1

Jia-Jia Lang, You Lv, Bostjan Kobe, Hongfei Chen, Yan Tan, Limei Chen, Xuechuan Wang, Pengbing Mi, Xing Zheng, Ying-Wu Lin

Summary: We discovered a series of C-5 pyrazole-modified pyrrolopyrimidine derivatives as JAK1-selective inhibitors, where the potential hydrogen bond between the pyrazole group and E966 in JAK1 is the key point that enhances JAK1 selectivity. These compounds exhibit 10-to 20-fold JAK1 selectivity over JAK2 in enzyme assays. Compound 12b also exhibits excellent JAK1 selectivity in Ba/F3-TEL-JAK cellular assays, and may be a viable lead compound for the development of highly JAK1-selective inhibitors for immune and inflammatory diseases, as indicated by metabolism studies and the results of the hair growth model in mice.

JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases

Nikos Kuehl, Johannes Lang, Mila M. Leuthold, Christian D. Klein

Summary: This study synthesized novel benzoxaborole inhibitors and evaluated their biological activity against the proteases of SARS-CoV-2 and dengue viruses. The most active compound showed strong inhibition against SARS-CoV-2 and significant inhibitory effects against dengue virus replication in cells.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

A novel N-heterocycles substituted oseltamivir derivatives as potent inhibitors of influenza virus neuraminidase: discovery, synthesis and biological evaluation

Jiwei Zhang, Chuanfeng Liu, Ruifang Jia, Xujie Zhang, Jian Zhang, Chiara Bertagnin, Anna Bonomini, Laura Guizzo, Yuanmin Jiang, Huinan Jia, Shuzhen Jia, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu

Summary: Introducing structurally diverse benzyl side chains at the C5-NH2 position of oseltamivir improves its binding affinity with neuraminidase and anti-influenza activity. We designed and synthesized novel oseltamivir derivatives with different N-heterocycle substituents that induce opening of the 150-loop of group-2 neuraminidases. Compound 6k showed broad-spectrum activity against wild-type neuraminidases and enhanced activity against H3N2 compared to oseltamivir carboxylate and zanamivir.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of 5-Aryl-2,4-diaminopyrimidine Compounds as Potent and Selective IRAK4 Inhibitors

Yan Chen, Rajinder Singh, Nan Lin, Vanessa Taylor, Esteban S. Masuda, Donald G. Payan

Summary: IRAK4 kinase plays a crucial role in regulating innate immune responses and inhibiting its activity can help control inflammatory disorders. Through screening and optimizing compounds, potent IRAK4 inhibitors have been discovered, and the design of new compounds has been facilitated by analyzing the protein structure. Optimization of the compounds resulted in improved selectivity over TAK1 kinase. Some compounds showed modest efficacy in animal model studies.

ACS MEDICINAL CHEMISTRY LETTERS (2022)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of indazole-pyridinone derivatives as a novel class of potent and selective MNK1/2 kinase inhibitors that protecting against endotoxin-induced septic shock

Agnieszka Dreas, Katarzyna Kucwaj-Brysz, Karolina Pyziak, Urszula Kulesza, Ewelina Wincza, Charles-Henry Fabritius, Kinga Michalik, Ewelina Gabor-Worwa, Aniela Golas, Mariusz Milik, Magdalena Masiejczyk, Eliza Majewska, Kazimiera Pysniak, Urszula Wojcik-Trechcinska, Zuzanna Sandowska-Markiewicz, Krzysztof Brzozka, Jerzy Ostrowski, Tomasz Rzymski, Michal Mikula

Summary: The study suggests that inhibition of the MNKs/eIF4E pathway can potentially treat cancer and inflammatory diseases. Compounds 24 and 26, selective and metabolically stable MNK1/2 inhibitors, effectively reduce the phosphorylation levels of eIF4E in pathological conditions, leading to improved survival rates and reduced proinflammatory cytokine levels in mice models.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity

Ruifang Jia, Jian Zhang, Chiara Bertagnin, Srinivasulu Cherukupalli, Wei Ai, Xiao Ding, Zhuo Li, Jiwei Zhang, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu

Summary: The structural modifications at the 150-cavity of influenza virus neuraminidases can result in more potent oseltamivir derivatives, with compound 5c showing the most promising activity. In vitro and in vivo studies demonstrated low cytotoxicity and no acute toxicity of 5c, indicating its potential as a drug candidate.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of novel N-benzylbenzamide derivatives as tubulin polymerization inhibitors with potent antitumor activities

Huajian Zhu, Wenlong Li, Wen Shuai, Yang Liu, Limei Yang, Yuchen Tan, Tiandong Zheng, Hong Yao, Jinyi Xu, Zheying Zhu, Dong-Hua Yang, Zhe-Sheng Chen, Shengtao Xu

Summary: Novel N-benzylbenzamide derivatives 20b and its corresponding disodium phosphate 20b-P show significant anti-cancer activity with excellent safety profile, making them promising anti-tubulin agents for further investigation in cancer therapy.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of Potent and Fast-Acting Antimalarial Bis-1,2,4-triazines

Daniel L. Priebbenow, Mitch Mathiew, Da-Hua Shi, Jitendra R. Harjani, Julia G. Beveridge, Marina Chavchich, Michael D. Edstein, Sandra Duffy, Vicky M. Avery, Robert T. Jacobs, Stephen Brand, David M. Shackleford, Wen Wang, Longjin Zhong, Given Lee, Erin Tay, Helena Barker, Elly Crighton, Karen L. White, Susan A. Charman, Amanda De Paoli, Darren J. Creek, Jonathan B. Baell

Summary: A series of novel 3,3'-disubstituted-5,5'-bi(1,2,4-triazine) compounds with potent in vitro activity against Plasmodium falciparum parasites were recently discovered. The new structure-activity relationship investigation led to the identification of second-generation highly potent antimalarial bis-triazines, with improved in vitro metabolic stability and a fast-killing profile. This new class of orally available antimalarial compounds is of considerable interest.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Virology

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

Amrita Saha, Badri Narayan Acharya, Manmohan Parida, Nandita Saxena, Jaya Rajaiya, Paban Kumar Dash

Summary: DCR 137 has been identified as a potential candidate for inhibiting the replication of CHIKV and Ross River virus, showing stronger antiviral activity compared to traditional drugs.

VIRUSES-BASEL (2023)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors

Jiahua Cui, Jinping Jia

Summary: The study identified a potent main protease inhibitor that can effectively suppress the replication of SARS-CoV-2, demonstrating potential value in drug discovery.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Reversible Monoacylglycerol Lipase Inhibitors: Discovery of a New Class of Benzylpiperidine Derivatives

Giulia Bononi, Miriana Di Stefano, Giulio Poli, Gabriella Ortore, Philip Meier, Francesca Masetto, Isabella Caligiuri, Flavio Rizzolio, Marco Macchia, Andrea Chicca, Amir Avan, Elisa Giovannetti, Chiara Vagaggini, Annalaura Brai, Elena Dreassi, Massimo Valoti, Filippo Minutolo, Carlotta Granchi, Juerg Gertsch, Tiziano Tuccinardi

Summary: The study reveals the potential of benzylpiperidine-based MAGL inhibitors in pancreatic cancer treatment. Inhibition of MAGL can reduce cell migration and promote apoptosis, synergizing with chemotherapy drugs.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Public, Environmental & Occupational Health

Short Report: Pre-Existing Cross-Reactive Antibodies to Avian Influenza H5N1 and 2009 Pandemic H1N1 in US Military Personnel

Sathit Pichyangkul, Somporn Krasaesub, Anan Jongkaewwattana, Arunee Thitithanyanont, Suwimon Wiboon-ut, Kosol Yongvanitchit, Amporn Limsalakpetch, Utaiwan Kum-Arb, Duangrat Mongkolsirichaikul, Nuanpan Khemnu, Rangsini Mahanonda, Jean-Michel Garcia, Carl J. Mason, Douglas S. Walsh, David L. Saunders

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2014)

添加到收藏夹

Article Chemistry, Multidisciplinary

A Secondary Sialic Acid Binding Site on Influenza Virus Neuraminidase: Fact or Fiction?

Jimmy C. C. Lai, Jean-Michel Garcia, Jeffrey C. Dyason, Raphael Boehm, Paul D. Madge, Faith J. Rose, John M. Nicholls, J. S. Malik Peiris, Thomas Haselhorst, Mark von Itzstein

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2012)

添加到收藏夹

Article Pharmacology & Pharmacy

Development of a multiplex phenotypic cell-based high throughput screening assay to identify novel hepatitis C virus antivirals

Hee-Young Kim, Xiaolan Li, Christopher T. Jones, Charles M. Rice, Jean-Michel Garcia, Auguste Genovesio, Michael A. E. Hansen, Marc P. Windisch

ANTIVIRAL RESEARCH (2013)

添加到收藏夹

Article Infectious Diseases

Transmission of pandemic influenza H1N1 (2009) in Vietnamese swine in 2009-2010

Karen Trevennec, Lucas Leger, Faouzi Lyazrhi, Eugenie Baudon, Chung Yan Cheung, Francois Roger, Malik Peiris, Jean-Michel Garcia

INFLUENZA AND OTHER RESPIRATORY VIRUSES (2012)

添加到收藏夹

Article Infectious Diseases

Investigation of the binding and cleavage characteristics of N1 neuraminidases from avian, seasonal, and pandemic influenza viruses using saturation transfer difference nuclear magnetic resonance

Jean-Michel Garcia, Jimmy C. C. Lai, Thomas Haselhorst, Ka Tim Choy, Hui-Ling Yen, Joseph S. M. Peiris, Mark von Itzstein, John M. Nicholls

INFLUENZA AND OTHER RESPIRATORY VIRUSES (2014)

添加到收藏夹

Article Pharmacology & Pharmacy

Herbal tea extracts inhibit Cytochrome P450 3A4 in vitro

Sophie Dufay, Alan Worsley, Aymeric Monteillier, Charlotte Avanzi, Jaclyn Sy, Ting Fat Ng, Jean-Michel Garcia, Man-Fai Lam, Paul Vanhoutte, Ian C. K. Wong

JOURNAL OF PHARMACY AND PHARMACOLOGY (2014)

添加到收藏夹

Article Chemistry, Organic

Copper(I)-Mediated Cascade Reactions: An Efficient Approach to the Synthesis of Functionalized Benzofuro[3,2-d]pyrimidines

Bo Chao, Shijun Lin, Qingdong Ma, Dong Lu, Youhong Hu

ORGANIC LETTERS (2012)

添加到收藏夹

Article Chemistry, Organic

Synthesis of Chromeno[2,3-d]imidazol-9(1H)-ones via Tandem Reactions of 3-lodochromones with Amidines Involving Copper-Catalyzed C-H Functionalization and C-O Bond Formation

Jia Sheng, Bo Chao, Hong Chen, Youhong Hu

ORGANIC LETTERS (2013)

添加到收藏夹

Article Multidisciplinary Sciences

Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial

Delia Bethell, David Saunders, Anan Jongkaewwattana, Jarin Kramyu, Arunee Thitithayanont, Suwimon Wiboon-ut, Kosol Yongvanitchit, Amporn Limsalakpetch, Utaiwan Kum-Arb, Nichapat Uthaimongkol, Jean Michel Garcia, Ans E. Timmermans, Malik Peiris, Stephen Thomas, Anneke Engering, Richard G. Jarman, Duangrat Mongkolsirichaikul, Carl Mason, Nuanpan Khemnu, Stuart D. Tyner, Mark M. Fukuda, Douglas S. Walsh, Sathit Pichyangkul

PLOS ONE (2013)

添加到收藏夹

Article Multidisciplinary Sciences

Identification of a Novel Sulfonamide Non-Nucleoside Reverse Transcriptase Inhibitor by a Phenotypic HIV-1 Full Replication Assay

Tae-Hee Kim, Yoonae Ko, Thierry Christophe, Jonathan Cechetto, Junwon Kim, Kyoung-Ae Kim, Annette S. Boese, Jean-Michel Garcia, Denis Fenistein, Moon Kyeong Ju, Junghwan Kim, Sung-Jun Han, Ho Jeong Kwon, Vincent Brondani, Peter Sommer

PLOS ONE (2013)

添加到收藏夹

Article Microbiology

Evaluation of serological tests for H5N1 avian influenza on field samples from domestic poultry populations in Vietnam: Consequences for surveillance

S. Desvaux, J. M. Garcia, T. D. Nguyen, S. A. Reid, N. A. Bui, F. Roger, S. Fenwick, J. S. M. Peiris, T. Ellis

VETERINARY MICROBIOLOGY (2012)

添加到收藏夹

Article Medical Laboratory Technology

Automated and simplified identification of normal and abnormal plasma cells in Multiple Myeloma by flow cytometry

Elina Alaterre, Sebastien Raimbault, Jean-Michel Garcia, Thierry Reme, Guilhem Requirand, Bernard Klein, Jerome Moreaux

CYTOMETRY PART B-CLINICAL CYTOMETRY (2018)

添加到收藏夹

Meeting Abstract Pharmacology & Pharmacy

Inhibition of cyclosporine and sirolimus metabolism by herbal teas

S. Dufay, A. Monteillier, C. Avanzi, T. F. Ng, J. -M. Garcia, M. -F. Lam, I. C. K. Wong, A. Worsley

INTERNATIONAL JOURNAL OF CLINICAL PHARMACY (2013)

添加到收藏夹

暂无数据

© Peeref 2019-2024. All rights reserved.