- Expedient discovery for novel antifungal leads targeting succinate dehydrogenase: Pyrazole-4-formylhydrazide derivatives bearing a diphenyl ether fragment
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The pyrazole-4-carboxamide scaffold containing a flexible amide chain has emerged as the molecular skeleton of highly efficient agricultural fungicides targeting succinate dehydrogenase (SDH). Based on the above vital structural features of succinate dehydrogenase inhibitors (SDHI), three types of novel pyrazole-4-formylhydrazine derivatives bearing a diphenyl ether moiety were rationally conceived under the guidance of a virtual docking comparison between bioactive molecules and SDH. Consistent with the virtual verification results of a molecular docking comparison, the in vitro antifungal bioassays indicated that the skeleton structure of title compounds should be optimized as an N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide scaffold. Strikingly, N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide derivatives 11o against Rhizoctonia solani, 11m against Fusarium graminearum, and 11g against Botrytis cinerea exhibited excellent antifungal effects, with corresponding EC50 values of 0.14, 0.27, and 0.52 μg/mL, which were obviously better than carbendazim against R. solani (0.34 μg/mL) and F. graminearum (0.57 μg/mL) as well as penthiopyrad against B. cinerea (0.83 μg/mL). The relative studies on an in vivo bioassay against R. solani, bioactive evaluation against SDH, and molecular docking were further explored to ascertain the practical value of compound 11o as a potential fungicide targeting SDH. The present work provided a non-negligible complement for the structural optimization of antifungal leads targeting SDH.
- Chen, Min,Li, Guohua,Lu, Aimin,Qiu, Lingling,Wang, An,Wang, Xiaobin,Xue, Wei,Yang, Chunlong
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p. 14426 - 14437
(2020/12/22)
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- Novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety as potent antifungal agents: synthesis, crystal structure, biological evaluation and a 3D-QSAR study
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Based on the active substructure combination principle, twenty-four novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety were designed, synthesized, and evaluated for their antifungal activity. Their structures were confirmed using 1H NMR, 13C NMR, and HR-MS spectra. The single-crystal structure of compound 8a was analyzed emphatically using X-ray diffraction. The antifungal activities against Fusarium graminearum, Botrytis cinerea, and Rhizoctonia solani were evaluated in vitro. The results of the bioassays revealed that most of the target compounds showed obvious fungicidal activity. Strikingly, the compound 7c exhibited the most potent activity with EC50 values of 0.74, 0.68, and 0.85 μg mL?1 against the above three plant pathogenic fungi, respectively. The compounds 7c, 8d, and 8g showed significant bioactivity against R. solani with EC50 values of 0.85, 0.25, and 0.96 μg mL?1, respectively. In addition, CoMFA and CoMSIA molecular modeling was performed for a 3D-QSAR study, and presented a good predictive ability with q2 values of 0.575 and 0.667, and r2 values of 0.961 and 0.962, respectively. The results provide useful information for guiding the design and synthesis of novel potent pyrazole derivatives with good antifungal activity.
- Jiao, Jian,Wang, An,Chen, Min,Wang, Meng-Qi,Yang, Chun-Long
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p. 6350 - 6360
(2019/04/25)
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- Containing substituted 1, 3, 4-thiadiazole sulfide pyrazole amide and pyrazole imine derivatives and preparation method and application
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The invention discloses pyrazole amide and pyrazole imine derivatives containing substituted 1, 3, 4-thiadiazole thioether as well as a preparation method and an application of the derivatives. The compounds have the structures as shown in formulae (I) and (II). The preparation method comprises the following steps: by taking substituted hydrazine as an initial raw material, carrying out closed loop, chlorine formylation, oxidation and chloro reaction to obtain pyrazole acyl chloride; carrying out a reaction on 2-amino-5-mercapto-1, 3, 4-thiadiazole and substituted benzyl chloride to obtain 2-amino-5-substituted 1, 3, 4-thiadiazole thioether; and then, carrying out a substitution reaction on 2-amino-5-substituted 1, 3, 4-thiadiazole thioether and substituted pyrazole acyl chloride to obtain the pyrazole amide compound (I) containing substituted 1, 3, 4-thiadiazole thioether; by taking substituted hydrazine as an initial raw material, carrying out closed loop and chlorine formylation to obtain pyrazole aldehyde; carrying out an additive elimination reaction on pyrazole aldehyde and 2-amino-5-mercapto-1, 3, 4-thiadiazole under a backflow condition of anhydrous ethanol to obtain 2-substituted pyrazole imidogen-5-mercapto-1, 3, 4-thiadiazole; and then carrying out a reaction on 2-substituted pyrazole imidogen-5-mercapto-1, 3, 4-thiadiazole and substituted benzyl chloride to generate the pyrazole imine compound (II) containing substituted 1, 3, 4-thiadiazole thioether. The compounds disclosed by the invention have a good inhibiting effect on tobacco mosaic virus and can be used for preparing anti-plant virus drugs.
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Paragraph 0091; 0092; 0093
(2016/11/24)
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- N,N-Dialkyl-N′-chlorosulfonyl chloroformamidines in heterocyclic synthesis. part IX.* novel triazolo-fused thiatriazoles and pyrazolo-fused oxathiazines
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N,N-dialkyl-N′-chlorosulfonyl chloroformamidines 1 reacted with 4-substituted urazoles 2 to give [1,2,4]triazolo[1,2-b] [1,2,3,5]thiatriazoles 3 in a selective 1,2-NN dinucleophilic mode of reaction.The reaction of 1 with N1-substituted pyrazol-5-ones 4 afforded pyrazolo[4,3-e][1,4,3] oxathiazines 5 via selective 1,3-CCO dinucleophilic substitution. Compounds 3 and 5 were the sole products isolated from the respective reactions and both represent new ring systems. CSIRO 2010.
- Forsyth, Craig M.,Francis, Craig L.,Jahangiri, Saba,Liepa, Andris J.,Perkins, Michael V.,Young, Anna P.
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scheme or table
p. 785 - 791
(2011/07/31)
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