A drug-likeness toolbox facilitates ADMET study in drug discovery
作者:
Jia, Chen-Yang
* ;Li, Jing-Yi;Hao, Ge-Fei;Yang, Guang-Fu
( 杨光富 )
期刊:
Drug Discovery Today ,2020年25(1):248-258 ISSN:1359-6446
通讯作者:
Jia, Chen-Yang
作者机构:
[Yang, Guang-Fu; Li, Jing-Yi; Jia, Chen-Yang; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Hao, Ge-Fei] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.;[Hao, Ge-Fei] Guizhou Univ, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn, Minist Educ,Res & Dev Ctr Fine Chem, Guiyang 550025, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China.
通讯机构:
[Jia, Chen-Yang] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要:
Undesirable pharmacokinetic (PK) properties or unacceptable toxicity are the main causes of the failure of drug candidates at the clinical trial stage. Since the concept of drug-likeness was first proposed, it has become an important consideration in the selection of compounds with desirable bioavailability during the early phases of drug discovery. Over the past decade, online resources have effectively facilitated drug-likeness studies in an economical and time-efficient manner. Here, we provide a comprehensive summary and comparison of current accessible online resources, in terms of their key features, application fields, and performance for in silico drug-likeness studies. We hope that the assembled toolbox will provide useful guidance to facilitate future in silico drug-likeness research.
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英文
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An overview of spirooxindole as a promising scaffold for novel drug discovery
作者:
Zhou, Li-Ming;Qu, Ren-Yu;Yang, Guang-Fu
* ( 杨光富 )
期刊:
Expert Opinion on Drug Discovery ,2020年15(5):603-625 ISSN:1746-0441
通讯作者:
Yang, Guang-Fu
( 杨光富 )
作者机构:
[Yang, Guang-Fu; Qu, Ren-Yu; Zhou, Li-Ming] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan, Peoples R China.
通讯机构:
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan, Peoples R China.
关键词:
Spirooxindole;natural products;bioactivity;anticancer;antimicrobial;structure-activity relationship
摘要:
Introduction: Spirooxindole, a unique and versatile scaffold, has been widely studied in some fields such as pharmaceutical chemistry and synthetic chemistry. Especially in the application of medicine, quite a few compounds featuring spirooxindole motif have displayed excellent and broad pharmacological activities. Many identified candidate molecules have been used in clinical trials, showing promising prospects. Areas covered: This article offers an overview of different applications and developments of spirooxindoles (including the related natural products and their derivatives) in the process of drug innovation, including such as in anticancer, antimicrobial, anti–inflammatory, analgesic, antioxidant, antimalarial, and antiviral activities. Furthermore, the crucial structure-activity relationships, molecular mechanisms, pharmacokinetic properties, and main synthetic methods of spirooxindoles-based derivatives are also reviewed. Expert opinion: Recent progress in the biological activity profiles of spirooxindole derivatives have demonstrated their significant position in present-day drug discovery. Furthermore, we believe that the multidirectional development of novel drugs containing this core scaffold will continue to be the research hotspot in medicinal chemistry in the future. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
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英文
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PALLADIUM-CATALYZED CROSS-COUPLING REACTIONS: A POWERFUL TOOL FOR THE SYNTHESIS OF AGROCHEMICALS
作者:
Devendar, Ponnam;Qu, Ren-Yu;Kang, Wei-Ming;He, Bo;Yang, Guang-Fu
* ( 杨光富 )
期刊:
Journal of Agricultural and Food Chemistry ,2018年66(34):8914-8934 ISSN:0021-8561
通讯作者:
Yang, Guang-Fu
( 杨光富 )
作者机构:
[Yang, Guang-Fu; Devendar, Ponnam; Kang, Wei-Ming; Qu, Ren-Yu; He, Bo] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Hubei, Peoples R China.;[Yang, Guang-Fu; Devendar, Ponnam; Kang, Wei-Ming; Qu, Ren-Yu; He, Bo] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Hubei, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.
通讯机构:
[Yang, Guang-Fu] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Hubei, Peoples R China.;Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Hubei, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.
关键词:
agrochemical;herbicide;fungicide;cross-coupling;transition metal;palladium
摘要:
Pd-catalyzed cross-coupling reactions have become essential tools for the construction of carbon-carbon and carbon-heteroatom bonds. Over the last three decades, great efforts have been made with cross-coupling chemistry in the discovery, development, and commercialization of innovative new pharmaceuticals and agrochemicals (mainly herbicides, fungicides, and insecticides). In view of the growing interest in both modern crop protection and cross-coupling chemistry, this review gives a comprehensive overview of the successful applications of various Pd-catalyzed cross-coupling methodologies, which have been implemented as key steps in the synthesis of agrochemicals (on R&D and pilot-plant scales) such as the Heck, Suzuki, Sonogashira, Stille, and Negishi reactions, as well as decarboxylative, carbonylative, α-arylative, and carbon-nitrogen bond bond-forming cross-coupling reactions. Some perspectives and challenges for these catalytic coupling processes in the discovery of agrochemicals are briefly discussed in the final section. The examples chosen demonstrate that cross-coupling chemistry approaches open-up new, low-cost, and more efficient industrial routes to existing agrochemicals, and such methods also have the capability to lead the new generation of pesticides with novel modes of action for sustainable crop protection. © 2018 American Chemical Society.
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英文
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A review on recent developments of indole-containing antiviral agents
作者:
Zhang, Ming-Zhi;Chen, Qiong
* ;Yang, Guang-Fu
( 杨光富 )
期刊:
European Journal of Medicinal Chemistry ,2015年89:421-441 ISSN:0223-5234
通讯作者:
Chen, Qiong
作者机构:
[Yang, Guang-Fu; Zhang, Ming-Zhi; Chen, Qiong] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
通讯机构:
[Chen, Qiong] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
关键词:
Indole;Antiviral activity;Entry and fusion inhibitor;Reverse transcriptase inhibitor;Integrase inhibitor;Protease inhibitor;Polymerase inhibitor;Natural product
摘要:
Indole represents one of the most important privileged scaffolds in drug discovery. Indole derivatives have the unique property of mimicking the structure of peptides and to bind reversibly to enzymes, which provide tremendous opportunities to discover novel drugs with different modes of action. There are seven indole-containing commercial drugs in the Top-200 Best Selling Drugs by US Retail Sales in 2012. There are also an amazing number of approved indole-containing drugs in the market as well as compounds currently going through different clinical phases or registration statuses. This review focused on the recent development of indole derivatives as antiviral agents with the following objectives: 1) To present one of the most comprehensive listings of indole antiviral agents, drugs on market or compounds in clinical trials; 2) To focus on recent developments of indole compounds (including natural products) and their antiviral activities, summarize the structure property, hoping to inspire new and even more creative approaches; 3) To offer perspectives on how indole scaffolds as a privileged structure might be exploited in the future. © 2014 Elsevier Masson SAS.
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英文
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