- Synthesis and nematicidal activity of piperazinedione derivatives based on the natural product Barettin
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Nematodes are serious constraints of crop production worldwide. However, the traditional nematicides suffer from the side-effects, including environmental and human toxicity. Herein, more than 70 novel piperazinedione derivatives based on the natural product Barettin were synthesized and evaluated against the root-knot nematode Meloidogyne incognita (M. incognita). While most of synthesized compounds exhibited certain nematicidal activity at high concentration, the best one showed a nematicidal activity of 75% at 2.4 μmol/L.
- Sun, Haiyang,Li, Hui,Wang, Jiayi,Song, Gonghua
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p. 977 - 980
(2017/11/16)
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- Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors
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VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti-proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4.
- Sun, Ying,Shan, Yuanyuan,Li, Chuansheng,Si, Ru,Pan, Xiaoyan,Wang, Binghe,Zhang, Jie
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p. 373 - 385
(2017/10/16)
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- N-fluorinated phenyl-N′-pyrimidyl urea derivatives: Synthesis, biological evaluation and 3D-qsar study
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With the increase of herbicide-resistant weeds, novel, more selective and even more potent herbicides to control weeds are needed. In this paper, a series of N-fluorinated phenyl-N′-pyrimidyl urea derivatives were synthesized and screened for their herbicidal activities against Amaranthus retroflexus (AR) and Setaria viridis (SV). Compound 25 (N-(3-trifluoromethylphenyl)-N′-(2- amino-4-chloro-6-methylpyrimidyl) urea) exhibited marked herbicidal activity against SV (IC50 = 11.67 mg/L) and is more potent than bensulfuron (IC50 = 27.45 mg/L), a commercially available herbicide. A statistically significant CoMFA model with high prediction abilities (q 2 = 0.869, r2 = 0.989) was obtained.
- Yue, Xia-Li,Li, Hu,Liu, Shuang-Shuang,Zhang, Qing-Ye,Yao, Jing-Jing,Wang, Fei-Yan
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p. 1069 - 1072
(2014/08/18)
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- Synthesis and crystal structure of N-(3-benzylamino-2-cyano-3- methylthioacrylyl)-N′-(substituted phenyl)ureas
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Phenylurea groups were introduced into the frame of traditional cyanoacrylate and a series of N-(3-benzylamino-2-cyano-3-methylthioacrylyl)- N′-(substituted phenyl)ureas were synthesized. All compounds are new and their structures were confirmed by 1H NMR, 13C NMR and mass spectral analyses.
- Zhong, Shi Hua,Fan, Ming Liang,Liu, Bing Yu,Wei, Dong Mei,Liu, Jian Bing
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p. 295 - 300
(2013/07/27)
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- Structural optimization of a CXCR2-directed antagonist that indirectly inhibits γ-secretase and reduces Aβ
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Amyloid β (Aβ), a key molecule in the pathogenesis of Alzheimer's disease (AD), is derived from the amyloid precursor protein (APP) by sequential proteolysis via β- and γ-secretases. Because of their role in generation of Aβ, these enzymes have emerged as important therapeutic targets for AD. In the case of γ-secretase, progress has been made towards designing potent inhibitors with suitable pharmacological profiles. Direct γ-secretase inhibitors are being evaluated in clinical trials and new strategies are being explored to block γ-secretase activity indirectly as well. In this regard, we have previously reported an indirect regulation of γ-secretase through antagonism of CXCR2, a G-protein coupled receptor (GPCR). We demonstrated that N-(2-hydroxy-4-nitrophenyl)-N′-(2-bromophenyl)urea (SB225002), a selective inhibitor of CXCR2 also plays a role in an indirect inhibition of γ-secretase. Furthermore, we reported a ~5-fold difference in the selective inhibition of APP versus Notch processing via γ-secretase following treatment with SB225002. Herein we describe the synthesis and optimization of SB225002. By determination of the structure-activity relationship (SAR), we derived small molecules that inhibit Aβ40 production with IC50 values in the sub-micromolar range in a cell-based assay and also validated the potential of CXCR2 as a new target for therapeutic intervention in AD.
- Bakshi, Pancham,Jin, Chao,Broutin, Pierre,Berhane, Beniam,Reed, Jon,Mullan, Michael
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experimental part
p. 8102 - 8112
(2010/03/24)
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- Organosilicon synthesis of isocyanates: I. Synthesis of isocyanates of the furan, thiophene, and mono-and polyfluorophenyl series
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A convenient synthesis of known and unknown isocyanates of the furan, thiophene, and mono-and polyfluorophenyl series, involving silylation of starting amines with hexamethyldisilazane or chlorotrimethylsilane, followed by phosgenation of the resulting N-silyl-substituted amines. An unusual high-temperature rearrangement of 3-(methoxycarbonyl)-4,5-dimethylthiophene-2-yl isocyanate into its 5-ethyl isomer. ortho-Fluorine substituent in anilines decreases the yield of isocyanates, whereas 2,3,5,6-tetrafluorophenyl isocyanate exists for only a short time as a 5% toluene solution. Pleiades Publishing, Inc. 2006.
- Lebedev,Lebedeva,Sheludyakov,Ovcharuk,Kovaleva,Ustinova
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p. 110 - 115
(2008/01/27)
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