Silicon-Containing Complex II Acaricides-Design, Synthesis, and Pharmacological Optimization

Bioisosteric replacement has been proven to be a powerful strategy in life science research. In this review, general aspects of carbon-silicon bioisosteric substitution and its applications in pharmaceutical and crop protection research are described. Carbon and their silicon analogues possess similar intrinsic properties. Replacing carbon with silicon in pharmaceuticals and pesticides has shown to result in positive effects on efficacy and selectivity, physicochemical properties, and bioavailability and also to eliminate or improve human or environmental safety properties as well as to provide novelty and new intellectual property in many cases. Furthermore, the application of carbon-silicon substitution in the search for new complex II acaricides is highlighted. This research led to the discovery of sila-cyflumetofen 23a and other silicon-containing analogues of cyflumetofen that match or exceed the acaricidal activity of cyflumetofen. The molecular design strategy, synthetic aspects, biological activity, computational modeling work, and structure-activity relationships will be discussed.

Automated summary

Bioisosteric replacement is a powerful strategy in life science research. The substitution of carbon with silicon has shown positive effects on efficacy and safety properties in pharmaceutical and crop protection research. The application of carbon-silicon substitution has led to the discovery of new silicon-containing analogues with improved acaricidal activity. This review discusses molecular design, synthesis, and structure-activity relationships in carbon-silicon bioisosteric substitution.