摘要：
In order to search novel agrochemicals with higher antifungal activity, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives bearing 1,3,4-oxadiazole moieties were designed and synthesized. Their antifungal activities against Rhizoctonia solani were evaluated in vitro. By determining the EC(50) values of all the newly synthesized compounds and 10 formerly synthesized compounds, compound 8r, 2-((5-(sec-butylthio)1,3,4-oxadiazol-2-yl)-methylthio)-5-dimethyl-1,2,4-triazolo-[1,5-a]pyrimidine, was found to display the highest antifungal activity (EC(50) = 6.57 mu g mL(-1)). Based on the quantitative structure-activity relationships analyses, 2-(1-(5-(sec-butylthio)- 1,3,4-oxadiazol-2-yl)ethylthio)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (9j) was designed and synthesized, which was found to display much higher activity (EC50 = 3.34 mu g mL(-1)) than compound 8r and the control. To further explore the comprehensive structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed and a statistically reliable model with good predictive power (r(2) = 0.929, q(2) = 0.588) was achieved on the basis of the common substructure-based alignment. According to the CoMFA model, the structure-antifungal activity relationship was explained reasonably. (c) 2007 Elsevier Masson SAS. All rights reserved.
期刊：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2015年89:421-441 ISSN：0223-5234
通讯作者：
Chen, Qiong;Yang, Guang-Fu
作者机构：
[Yang, Guang-Fu; Zhang, Ming-Zhi] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China;[Yang, Guang-Fu] Collaborative Innovation Center of Chemical Science and Engineering, Tianjing 30071, PR China. Electronic address: gfyang@mail.ccnu.edu.cn;[Chen, Qiong] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address: qchen@mail.ccnu.edu.cn
通讯机构：
[Yang, Guang-Fu] Collaborative Innovation Center of Chemical Science and Engineering, Tianjing 30071, PR China. Electronic address:;[Chen, Qiong] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address:
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. (C) 2014 Elsevier Masson SAS. All rights reserved.
作者机构：
[ Yang, Guang-Fu ] Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 30071, China;[Li, Jun ; Yang, Wen-Chao ; Zhang, Chun-Fang ; Yang, Shu-Hou ] Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China
通讯机构：
[Yang, WC] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
A series of chromone derivatives bearing diverse dithiocarbamate moieties were designed and synthesized via a three-component reaction protocol. Their in vitro antitumor activities were evaluated by MTT method against HCCLM-7, Hela, MDA-MB-435S, SW-480, Hep-2 and MCF-7. Two compounds (3-chloro-4-oxo-4H-chromen-2-yl)methyl piperidine-1-carbodithioate (Iq) and (6-chloro-4-oxo-4H-chromen-3yl)methyl piperidine-1-carbodithioate (IIu), were identified as the most promising candidate due to their high potency and broad-spectrum. Further flow-activated cell sorting analysis revealed that compounds Iq and IIu arrest the cell cycle of SW-480 and MDA-MB-435s both in G(2)/M phase with dose-dependent effect and might display apoptosis-inducing effect on these tumor cell lines. (C) 2009 Elsevier Masson SAS. All rights reserved.
期刊：
Journal of the American Chemical Society,2009年132(1):185-194 ISSN：0002-7863
通讯作者：
Zhan, C.-G.(zhan@uky.edu)
作者机构：
[Guang-Fu Yang; Xiao-Lei Zhu; Pei-Liang Zhao] Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal UniVersity, Wuhan 430079, China;[Chang-Guo Zhan; Xiaoqin Huang] Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536, United States;[Jia-Wei Wu; Le Wang] MOE Key Laboratory of Bioinformatics, Department of Biological Sciences and Biotechnology, Tsinghua UniVersity, Beijing 100084, China
通讯机构：
[Zhan, CG] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, 725 Rose St, Lexington, KY 40536 USA.
摘要：
1-Acetyl-3,-5-diarylpyrazolines have received considerable interests from the fields of medicinal and agricultural chemistry due to their broad spectrum of biological activities. To discover new lead compounds exhibiting both fungicidal and insecticidal activities, a series of pyrazoline derivatives were designed and synthesized by introducing the beta-methoxyacrylate pharmacophore into the scaffold of 1-acetyl-3,5-diarylpyrazoline. The fungicidal activities against Pseudoperoniospora cubensis, Sphaerotheca fuliginea, Botrytis cinerea, and Rhizoctonia solani and the insecticidal activities against Aphis medicagini, Nilaparvata legen, Mythima separata, and Tetranychus cinnabarnus were screened. The most potent compound 13, 1-aceto-3-[m-[o-(E-1-methoxycarboxyl-2-methoxy)-1-yl]benzyloxy]phenyl-5-(benzo-[1 ,3]-dioxolyl)-4,5-dihydro- pyrazoline, was identified. Its fungicidal IC(50) values against P. cubensis and S. fuliginea are 26.6 and 57.6 microg mL(-1), respectively, while its insecticidal LC(50) value against M. separata is 26.6 microg mL(-1). These results indicated that compound 13 could be used as a lead for further developing new pyrazoline type products exhibiting both fungicidal and insecticidal activities.
期刊：
Journal of the American Chemical Society,2012年134(27):11168-11176 ISSN：0002-7863
通讯作者：
Wu, J.-W.(jiaweiwu@mail.tsinghua.edu.cn)
作者机构：
[Yang, Guang-Fu; Yang, Wen-Chao; Zhu, Xiao-Lei; Li, Hui; Hao, Ge-Fei; Wang, Fu] Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, China;[Huang, Li-Shar; Berry, Edward A] Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, United States;[Li, Hui; Wu, Jia-Wei] MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
通讯机构：
[Wu, JW] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.
关键词：
Binding affinities - Critical challenges - Cytochrome bc - Cytochrome c - Drug discovery - Drug discovery methods - High-throughput - Membrane proteins - Molecular basis - Potent compounds - Screening techniques - Ubiquinol - Virtual Screening
摘要：
Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has been identified as one of the most significant action targets for a large chemically diverse family of herbicides that exhibit some interesting characteristics, such as low use rate, low toxicity to mammals, and low environmental impact. As a continuation of research work on the development of new PPO inhibitors, some benzothiazole analogues of oxadiargyl, an important PPO-inhibiting commercial herbicide, were designed and synthesized by ring-closing of the substituents at the C-4 and C-5 positions. The bioassay results indicated that the series 8, 9, and 10 have good PPO inhibition activity with k(i) values ranging from 0.25 to 18.63 microM. Most interestingly, 9l, ethyl 2-((5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)sul fanyl) propanoate, was identified as the most promising candidate due to its high PPO inhibition effect (k(i) = 1.42 microM) and broad spectrum postemergence herbicidal activity at the concentration of 37.5 g of ai/ha.
摘要：
On the basis of the principle of combination of active structural moieties, a modified and efficient synthetic method for three series of novel indole-based 1,3,4-oxadiazoles is described. Bioassays conducted at Syngenta showed that several of the synthesized compounds exhibit higher antifungal activity than pimprinine, the natural product which inspired this synthesis. Two main structural-alterations were found to broaden the spectrum of biological activity in most cases. Compounds 3g, 6c, 6e, 6h, 9d, 9e, 9h and 9m (Fig. 1) were identified as the most active on the biological assays, and will be studied further. (c) 2013 Elsevier Masson SAS. All rights reserved.
摘要：
The characteristics of low application rates, good crop selectivity, low residue and environmental safety exhibited by Protoporphyrinogen oxidase (PPO, EC 1.3.3.4)-inhibiting herbicides have attracted a world-wide research interests. As continuation of our research work on the development of new PPO inhibitors, a series of mono-carbonyl analogues of cyclic imides, N-phenyl pyrrolidin-2-ones and N-phenyl-1H-pyrrol- 2-ones, were designed and synthesized based on previously established DFT-QSAR results. The PPO inhibition activities of 29 newly synthesized compounds were tested and a predictive comparative molecular field analysis (CoMFA) model was established with the conventional correlation coefficient r(2) = 0.980 and the cross-validated coefficient q(2) = 0.518. According to the CoMFA model, the substituent effects on the PPO inhibition activity were explained reasonably. Further greenhouse assay showed that 2-(4-chloro-2-fluoro-5-propoxy-phenyl)-2,3,4,5,6,7-hexahydro-isoindol-1-one (C(6), k(i) = 0.095 mu M) and 2-(5-allyloxy-4-chloro-2-fluorophenyl)-2,3,4,5,6,7-hexahydro-isoindol-1-one (C(7), k(i) = 0.12 mu M) displayed excellent post-emergency herbicidal activity at the concentration of 150 g.ai/ha against seven tested weeds. Due to their high PPO inhibition effect and broad spectrum herbicidal activity, these two compounds have the potential for further study on crop selectivity and field trial. These results confirmed once again that only one of the carbonyl groups of cyclic imides is essential to the PPO inhibition activity. (C) 2010 Elsevier Ltd. All rights reserved.
摘要：
Triazolopyrimidine-2-sulfonamide belongs to a herbicide group called acetohydroxyacid synthase inhibitors. With the aim to discover new triazolopyrimidine sulfonanilide compounds with high herbicidal activity and faster degradation rate in soil, the methyl group of Flumetsulam (FS) was modified into a methoxy group to produce a new herbicidal compound, N-2,6-difluorophenyl-5-methoxy-1,2,4-triazolo[1,5-a] pyrimidine-2-sulfonamide (experimental code: Y6610). The enzymatic kinetic results indicated that compound Y6610 and FS have k(i) values of 3.31 x 10 (6) M and 3.60 x 10 (7) M against Arabidopsis thaliana AHAS, respectively. The 10-fold lower enzyme-inhibiting activity of Y6610 was explained rationally by further computational simulations and binding free energy calculations. In addition, compound Y6610 was found to display the same level in vivo post-emergent herbicidal activity as FS against some broad-leaf weeds and good safety to rice, maize, and wheat at the dosages of 75-300g ai/ha. Further determination of the half-lives in soil revealed that the half-life in soil of Y6610 is 3.9 days shorter than that of FS. The experimental results herein showed that compound Y6610 could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study. (C) 2009 Elsevier Ltd. All rights reserved.
期刊：
Journal of Agricultural and Food Chemistry,2012年60(18):4480-4491 ISSN：0021-8561
通讯作者：
Gu, Y.-C.(yucheng.gu@syngenta.com)
作者机构：
[ Yang, Guang-Fu ; Lin, Long ; Huang, Shao-Wei ; Wu, Qiong-You ] Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan 430079, China;[ Gu, Yu-Cheng ; Beattie, David ; Irwin, Dianne ; Mulholland, Nick ; Clough, John ] Syngenta Jealotts Hill International Research Centre, Bracknell, Berkshire RG42 6EY, United Kingdom
通讯机构：
[Gu, YC] Syngenta Jealotts Hill Int Res Ctr, Bracknell RG42 6EY, Berks, England.
关键词：
Anti-fungal activity - azaphilone - Bicyclic ring system - Cycloisomerizations - Free hydroxyl groups - Functionalized - Fungal pathogen - Natural products - Phenyl group - Quaternary centers - sclerotiorin - Sonogashira cross-coupling reaction - Structure activity relationships
作者机构：
[Guangfu Yang] Key Laboratory of Pesticide and Chemical Biology, Huazhong Normal University, Ministry of Education, Wuhan 430079, China;[Xuefeng Li; Yi Yang; Li Cheng; Zan Jiang; Bo Cai; Jinfeng Dong] College of Chemistry and Molecules Sciences, Wuhan University, Wuhan 430072, China
摘要：
The triazolopyrimidine-2-sulfonanilide, discovered from preparing bioisosteres of the sulfonylurea herbicides, is an important class of acetohydroxyacid synthase (AHAS, EC 4.1.3.18) inhibitors. At least over ten triazolopyrimidine sulfonanilides have been commercialized as herbicides for the control of broadleaf weeds and grass with cereal crop selectivity. Herein, a series of triazolopyrimidine-2-sulfonanilides were designed and synthesized with the aim of discovery of new herbicides with higher activity. The assay results of the inhibition activity of the synthesized compounds against Arabidopsis thatiana AHAS indicated that some compounds showed a little higher activity against flumetsulam (FS), the first commercial triazolopyrimidine-2-sulfonanilide-type herbicide. The k(i) values of two promising compounds 3d and 8h are respectively, 1.61 and 1.29 mu M, while that of FS is 1.85 mu M. Computational simulation results indicated the ester group of compound 3d formed hydrogen bonds with the surrounding residues Arg'198 and Ser653, which accounts for its 11.5-folds higher AHAS inhibition activity than Y6610. Further green house assay showed that compound 3d has comparable herbicidal activity as FS. Even at the concentration of 37.5 g.ai/ha, 3d showed excellent herbicidal activity against Galium aparine, Cerastium arvense, Chenopodium album, Amaranthus retroflexus, and R mu mex acetasa, moderate herbicidal activity against Polygonum humifusum, Cyperus iria, and Eclipta prostrate. The combination of in vitro and in vivo assay indicated that 3d could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study. (C) 2010 Elsevier Ltd. All rights reserved.
期刊：
Journal of Agricultural and Food Chemistry,2011年59(11):6172-6179 ISSN：0021-8561
通讯作者：
Xi, Z
作者机构：
[Yang, Guang-Fu; Jiang, Li-Li; Zuo, Yang; Wu, Qiong-You; Tan, Yin; Wang, Zhi-Fang] Key Laboratory of Pesticide and Chemical Biology, Central China Normal University, Ministry of Education, Wuhan 430079, China;[Xi, Zhen] State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
通讯机构：
[Xi, Z] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.
作者机构：
[Yang, Guang-Fu; Peng, Da-Yong; Sun, Qi; Zhu, Xiao-Lei; Yang, Sheng-Gang] Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China;[Yang, Guang-Fu] Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 30071, PR China. Electronic address: gfyang@mail.ccnu.edu.cn;[Yang, Wen-Chao] Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address: tomyang@mail.ccnu.edu.cn
通讯机构：
[Yang, Guang-Fu] Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 30071, PR China. Electronic address:;[Yang, Wen-Chao] Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address:
摘要：
Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (K-i = 16.7 nM) against human AChE and about 2-fold lower potency (K-i = 16.1 nM) against BChE than tacrine (K-i = 35.7 nM for AChE, K-i = 8.7 nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both A beta aggregation and beta-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery. (C) 2014 Elsevier Ltd. All rights reserved.
期刊：
JOURNAL OF CHEMICAL INFORMATION AND MODELING,2009年49(8):1936-1943 ISSN：1549-9596
通讯作者：
Zhna, C.-G.(gfyang@mail.ccnu.edu.cn)
作者机构：
[ Yang, Guang-Fu ; Hao, Ge-Fei ; Zhu, Xiao-Lei ] Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, China;[ Zhna, Chang-Guo ] Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536, United States
通讯机构：
[Yang, GF] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan 430079, Peoples R China.
作者机构：
[Yang, Guangfu; Zhu, Fengxiang; Zhou, Shaolin; Zhu-Ge, Ling] Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan,Hubei, China;[Zhou, Shaolin] CCNU-uOttawa Joint Research Centre, Wuhan, China
通讯机构：
[Zhu, FX] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, 152 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China.
关键词：
Active catalyst - Catalyst system - Catalytic hydrogenation - Formates - Homogeneous catalysis - Iron complex - Low hydrogen pressure - Phosphine-free
