作者机构：
[He, Hongwu; Liu, Jianchao] Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.;[Ren, Qingyun] HEC Pharma Co LTD, New Drug Res Inst, Antiinfect Innovat Dept, Dongguan 523871, Guangdong, Peoples R China.
通讯机构：
[He, Hongwu] C;[Ren, Qingyun] H;Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.;HEC Pharma Co LTD, New Drug Res Inst, Antiinfect Innovat Dept, Dongguan 523871, Guangdong, Peoples R China.
摘要：
On the basis of previous study on 2-methylpyrimidine-4-ylamine derivatives I, further synthetic optimization was done to find potent PDHc-E1 inhibitors with antibacterial activity. Three series of novel pyrimidine derivatives 6, 11 and 14 were designed and synthesized as potential Escherichia coli PDHc-E1 inhibitors by introducing 1,3,4-oxadiazole-thioether, 2,4-disubstituted-1,3-thiazole or 1,2,4-triazol-4-amine-thioether moiety into lead structure I, respectively. Most of 6, 11 and 14 exhibited good inhibitory activity against E. coli PHDc-E1 (IC50 0.97-19.21 mu M) and obvious inhibitory activity against cyanobacteria (EC50 0.83-9.86 mu M). Their inhibitory activities were much higher than that of lead structure I. 11 showed more potent inhibitory activity against both E. coli PDHc-E1 (IC50 < 6.62 mu M) and cyanobacteria (EC50 < 1.63 mu M) than that of 6, 14 or lead compound I. The most effective compound 11d with good enzyme-selectivity exhibited most powerful inhibitory potency against E. coli PDHc-E1 (IC50 = 0.97 mu M) and cyanobacteria (EC50 = 0.83 mu M). The possible interactions of the important residues of PDHc-E1 with title compounds were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that 11d had more potent inhibitory activity than that of 14d or I due to its 1,3,4-oxadiazole moiety with more binding position and stronger interaction with Lsy392 and His106 at active site of E. coli PDHc-E1. (C) 2016 Elsevier Ltd. All rights reserved.
摘要：
GRAPHICAL ABSTRACT Synthesis and fungicidal activity of aryl(arylamino)methylphosphonic acids All authors Haiqin Wang, Hao Peng & Hongwu He https://doi.org/10.1080/10426507.2015.1119829 Published online:11 May 2016 ABSTRACT A series of aryl(arylamino)methylphosphonic acids were synthesized based on the previous work for the modification of alkylphosphonates. As key intermediates, α-aminophosphonates were synthesized with high yield by a three-component Kabachnik–Fields reaction under solvent-free conditions. The compounds were identified and characterized by infrared, 1H NMR, 13C NMR, mass spectrum, and elemental analyses. Their fungicidal activities against typical fungi occurring in the Chinese agro-ecosystems were evaluated. The results of preliminary bioassays showed that some of the title compounds exhibited moderate fungicidal activities against tomato late blight and cucumber fusarium wilt. For example, compound 3b showed 78% inhibitory activity against tomato late blight, and compound 3h possessed 86% inhibitory activity against cucumber fusarium wilt.
摘要：
[目的]为了获得具有除草剂应用价值的高活性化合物。[方法]以烃基膦酸酯为先导结构,对其含磷端以及桥链和芳基部分进行结构修饰,设计合成多个系列烃基膦酸酯类化合物。[结果]除草活性测试结果表明,在150 g ai/ha剂量下,多个化合物对芥菜、苘麻、反枝苋和醴肠等阔叶杂草表现出良好的抑制活性,除草活性与对照药剂氯酰草膦相当甚至更优。杀草谱测试结果表明数个化合物对阔叶杂草的防效与草甘膦相当。作物安全性评
通讯机构：
[He, HW; Feng, LL] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, 152 Luoyu Rd, Wuhan 430079, Peoples R China.
摘要：
In this study, a series of novel amide derivatives and sulfamide derivatives as potential E. coli PDHc E1 inhibitors were designed and synthesized by optimizing the linker between triazole and benzene ring moieties based on the structure of lead compound I as thiamin diphosphate (ThDP) analogs. Their inhibitory activity against E. coli PDHc E1 were examined in vitro and their inhibitory activity against microbial diseases were further evaluated. Most of these compounds exhibit good inhibitory activity against E. coli PHDc E1 (IC50 1.99 to 25.66 μM) and obvious antibacterial activity. 5a, 5c and 9i showed 90–100% antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Acidovorax avenae subsp. avenae (Aaa) and cyanobacteria. Sulfamide derivatives 9 showed more potent inhibitory activity against E. coli PDHc E1 (IC50 < 14 μM) than that of amide derivatives 5 or lead compound I. Especially 9d (IC50 = 2.95 μM) and 9k (IC50 = 1.99 μM) exhibited not only the most powerful inhibitory potency against E. coli PDHc E1, but also 9k showed 99% antibacterial activity against Aaa at 500 μg mL−1 and almost the best inhibition of 97% against cyanobacteria at 20 μg mL−1. Furthermore, the binding mode of 5d and 9d to E. coli PDHc E1 was analyzed by a molecular docking method. The possible interactions of 9d with the important residues of E. coli PDHc E1 were further verified via site-directed mutagenesis enzymatic assays, and fluorescence spectral analysis. Both theoretical and experimental results revealed that 9d could display a more powerful interaction than that of 5d or I by forming a hydrogen bond between a sulfamide linkage and residues Lsy392, Tyr599 and His106 at active site of E. coli PDHc E1. 9k, 9d and 9i with both potent enzyme inhibition and significant antibacterial activity, could be used as novel lead compounds for further optimization. These results proved that a series of compounds with potential antibacterial activity could be obtained by the biorational design of E. coli PDHc E1 inhibitors.
摘要：
A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50 values of 2.21 mu g/mL, 1.67 mu g/mL and 1.11 mu g/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide-hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest. (C) 2016 Elsevier Ltd. All rights reserved.
摘要：
A three-dimensional quantitative structure–activity relationship (3D-QSAR) study was performed on two different chemical series, which have great herbicidal activity, employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) techniques to further investigate the structural requirement for the dicotyledonous stem inhibition. The optimal CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q2) of 0.702, 0.726 and conventional coefficients (R2) of 0.980, 0.963, respectively. These models were validated by a set of six molecules that were not included in the training set. The CoMFA yielded comparable models for phosphonate and phosphinate derivatives highlighting the significance of steric and electrostatic fields toward dicotyledonous stem inhibitory activity. The CoMSIA models indicated the importance of electrostatic and hydrophobic fields toward dicotyledonous stem inhibitory activity. The CoMSIA steric and electrostatic field maps are in accordance with field distribution of CoMFA maps and consistent with structure–activity relationships.
期刊：
Journal of Heterocyclic Chemistry,2015年52(4):1260-1263 ISSN：0022-152X
通讯作者：
He, Hongwu
作者机构：
[He, Hongwu] Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.;Cent China Normal Univ, Coll Chem, Wuhan, Peoples R China.
通讯机构：
[He, Hongwu] C;Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.
期刊：
Journal of Heterocyclic Chemistry,2015年52(3):647-652 ISSN：0022-152X
通讯作者：
Ren, Qingyun
作者机构：
[He, Hongwu; Gu, Yucheng; Ren, Qingyun] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Li, Baoju; Xia, ShiYan] Chinese Acad Agr Sci, Inst Vegetables & Flowers, Beijing 100081, Peoples R China.;[Gu, Yucheng] Syngenta Jealotts Hill Int Res Ctr, Bracknell RG42 6EY, Berks, England.;[Ren, Qingyun] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, 152 Luoyu Rd, Wuhan 430079, Peoples R China.
通讯机构：
[Ren, Qingyun] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, 152 Luoyu Rd, Wuhan 430079, Peoples R China.
摘要：
Fifteen novel 2-alkylamino-3-aryl-8-cyano-5-methyl-7-(methylthio)-pyrido[4,3-d]pyrimidin-4(3H)-ones 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 6n, 6o were designed and have been successfully synthesized via tandem aza-Wittig and annulation reactions with the corresponding iminophosphoranes 4, aryl isocyanate, and amines in good yields. Their structures were clearly verified by IR spectroscopy, 1H-NMR spectroscopy, EI-MS, and elemental analysis, and in the case of compound 6i, further analyzed by single-crystal X-ray diffraction. The preliminary results of an in vivo bioassay showed that some compounds display moderate antifungal activity.
期刊：
Journal of Heterocyclic Chemistry,2015年52(1):173-179 ISSN：0022-152X
通讯作者：
Peng, Hao
作者机构：
[Peng, Hao] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan, Peoples R China.;Cent China Normal Univ, Coll Chem, Wuhan, Peoples R China.
通讯机构：
[Peng, Hao] C;Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan, Peoples R China.
摘要：
A series of novel O,O‐dimethyl 1‐(substituted phenoxyacetoxy)‐1‐(pyridin‐2‐yl or thien‐2‐yl)methylphosphonates 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 6n and 7a, 7b, 7c, 7d were synthesized. Their structures were confirmed by IR, 1H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal and fungicidal activities. For example, the title compounds 6a, 6c, 6l, 6m, and 7d possess 90–100% inhibition against most of the tested plants at the dosage of 1500 g ai/ha, whereas the title compounds 6b, 6g, 6h and 6n possess 92–100% inhibition against Fusarium oxysporum, Phyricularia grisea, Botrytis cinereapers, Gibberella zeae, Sclerotinia sclerotiorum, and Cercospora beticola at the concentration of 50 mg/L.
作者机构：
[Liu Jianchao; He Hongwu] Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.;[Ren Qingyun] Sunshine Lake Pharma Co Ltd, New Drug Res Inst, Antiinfect Innovat Dept, Dongguan 523871, Peoples R China.
通讯机构：
[Liu Jianchao] C;Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.
关键词：
多取代吡啶;六水合硝酸锌;β-二羰基化合物;杀菌活性;除草活性
摘要：
采用六水合硝酸锌作催化剂、少量的乙醇钠为助催化剂,使用无水乙醇作为溶剂,将2-氰基-3-烷胺基-3-氨基-丙烯腈(N,N-缩醛)与β-二羰基化合物一步关环生成了一系列目标化合物4-氨基-5-氰基-6-烷胺基吡啶衍生物.通过~1H NMR, IR, EI-MS,元素分析等方法对所合成的化合物进行了结构表征.代表化合物2-甲基-4-氨基-5-氰基-6-乙醇胺基- 3-乙氧羰基吡啶经单晶X衍射证实了结构.对合成的多取代吡啶衍生物化合物作了初步的农药活性测试,测试结果表明:所合成的多取代吡啶衍生物部分化合物表现出较好的杀菌活性,同时也对油菜和稗草具有一定的除草活性.
