Succinate-ubiquinone oxidoreductase (SQR, EC 1.3.5.1) catalyzes the oxidation of succinate to fumarate, and plays an important role in the tricarboxylic acid cycle. SQR has been identified as a novel target of a large family of agricultural fungicides. Until recently, many fungicides such as fluxapyroxad and isopyrazam are complex II inhibitors, and they belong to the carboxamide agrochemical class, which is a hotspot of current research. The commercial complex II fungicides include several structurally diverse groups, such as pyrazole-4-carboxamides, oxathiin-carboxamides, phenyl-benzamides, pyridine-carboxamides, thiazole-carboxamides, phenyl-oxo-ethyl-thiophene amide, pyridinyl-ethyl benzamides, furan-carboxamides. Among the existing commercial complex II inhibitors mentioned above, pyrazole-4-carboxamides have attracted considerable attention in the field of pesticide chemistry in recent years.  In addition, the benzooxazole derivatives are known to possess a wide range of biological activities, some of the derivatives have also been widely used in agriculture. And the introduction of the benzooxazole moiety might be an effective way to improve the protency of complex II inhibitor. Therefore, a series of benzooxazol-pyrazole-4-carboxamides were designed and synthesized via this strategy. These compounds showed good or excellent inhibitory activity against porcine complex II with the Ki values ranging from 0.208mM to 0.057mM, much higher than the commercial control of penthiopyrad and fluxapyroxad. To our knowledge, compound Y13405 (Ki =0.057mM) is so far known as one of the most potent inhibitors of complex II.

Design and synthesis of benzo[d]oxazol-5-yl)-1-methyl-1H-pyrazole-4-carboxamides as complex II inhibitors

248th National Meeting (2014)

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