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 of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid
-
Paragraph 0036; 0039-0040, (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: by taking 2, 2-difluoroacetyl halide as a raw material, performing addition with alpha, beta-unsaturated ester, performing alkaline hydrolysis to obtain alpha-difluoroacetyl intermediate carboxylic acid, condensing and cyclizing the 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid with a methylhydrazine aqueous solution in the presence of a catalyst to obtain a 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid crude product, and recrystallizing to obtain a pure product of the 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The method has the advantages of simple operation, easily available raw materials, high reaction yield, reduction of isomers through a plurality of ways in the reaction process, and convenience in product purification.
Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid
-
Paragraph 0045-0053, (2020/07/13)
The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, and belongs to the field of pesticide organic synthesis. The preparation method comprises thefollowing steps: step 1, enabling 1-methyl-3-(trimethylsilyl) pyrazole to react with halogen to obtain 4-halogen-1-methyl-3-(trimethylsilyl) pyrazole; step 2, after exchange is conducted through a Grignard reagent, enabling the 4-halogen-1-methyl-3-(trimethylsilyl) pyrazole to react with chloroformate to obtain 1-methyl-3-trimethylsilyl-1H-pyrazole-4-carboxylic acid; step 3, then carrying out a heating reaction with bromine, so as to obtain 3-bromo-1-methyl-1H-pyrazole-4-carboxylic acid; and step 4, finally, carrying out heating coupling on the 3-bromo-1-methyl-1H-pyrazole-4-carboxylic acid and difluoromethylboronic acid by adopting a palladium catalyst, and performing recrystallization to obtain the 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The invention provides a new synthesis path for the synthesis of the compound, and has a potential industrial method prospect.