176969-34-9Relevant articles and documents
Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon-Silicon Switch Strategy
Wei, Ge,Huang, Ming-Wei,Wang, Wen-Jie,Wu, Yuan,Mei, Shu-Fen,Zhou, Li-Ming,Mei, Long-Can,Zhu, Xiao-Lei,Yang, Guang-Fu
, p. 3965 - 3971 (2021/05/04)
The carbon-silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel and patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is a promising fungicide candidate recently developed in China. We describe the synthesis of novel SDH inhibitors with enhanced fungicidal activity to enlarge the chemical space of flubeneteram by employing the C-Si switch strategy. Several of the thus formed flubeneteram-silyl derivatives exhibited improved fungicidal activity against porcine SDH compared with the lead compound flubeneteram and the positive controls. Disease control experiments conducted in a greenhouse showed that trimethyl-silyl-substituted compound W2 showed comparable and even higher fungicidal activities compared to benzovindiflupyr and flubeneteram, respectively, even with a low concentration of 0.19 mg/L for soybean rust control. Furthermore, compound W2 encouragingly performed slightly better control than azoxystrobin and was less active than benzovindiflupyr at the concentration of 100 mg/L against soybean rust in field trials. The computational results showed that the silyl-substituted phenyl moiety in W2 could form strong van der Waals (VDW) interactions with SDH. Our results indicate that the C-Si switch strategy is an effective method for the development of novel SDH inhibitors.
Preparation method and application of pyrazole derivative
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Paragraph 0037-0038, (2020/05/08)
The invention relates to a preparation method of a pyrazole derivative. The compound shown in the formula I reacts with a silanization reagent shown in a formula II to generate an intermediate productshown in a formula III, the intermediate product shown in the formula III reacts with a halogenated acid derivative shown in a formula IV to generate a halogenated compound shown in a formula V, andthe halogenated compound shown in the formula V reacts under acidic conditions to generate a pyrazole derivative shown in a formula VI. The preparation method of the pyrazole derivative is suitable for industrial production.
Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid
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Paragraph 0022; 0028-0029, (2020/07/15)
The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, and belongs to the technical field of organic synthesis. The preparation method comprises thefollowing steps: reacting N-methyl-3-aminopyrazole as a raw material with bromine/iodine to replace pyrazole at site 4, then carrying out diazotizing and coupling with potassium difluoromethyl trifluoroborate to obtain 4-bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole, then performing Grignard exchange by adopting isopropyl magnesium chloride and the like, and performing reaction with carbon dioxide to obtain 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The method is simple and convenient to operate, the total yield of the three steps is as high as 64%, the product purity can reach 99.5% or above, the situation in which isomers exist in a traditional process is avoided, and the method has potential process amplification prospects.