Crop protection chemistry has come a long way from its "alchemic" beginnings in the late 19th century to a high-tech science that supports the sustainable production of food, feed, and fiber for a rapidly growing population. Cutting-edge developments in the design and synthesis of agrochemicals help to tackle today's challenges of weed and pest resistance, higher regulatory safety margins, and higher cost of goods with the invention of selective, environmentally benign, low use rate, and cost-effective active ingredients.

Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded chemical features has been underestimated or even overlooked. In the course of our research in the agrochemical area, we have concluded that in many cases such leads are actually nonoptimizable because they either contain what are now recognized as pan assay interference compounds (PAINS) or other promiscuous groups. This article is aimed at highlighting the pitfalls we have encountered and hopefully to steer other research groups away from them.

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