AbstractBACKGROUNDWe hypothesized that the exploration of chemical space around compounds with reported insecticidal activity could be a viable strategy for discovering novel, insecticidally active areas of chemistry.RESULTSA series of thioureas and isothioureas were prepared as part of a scaffold‐hopping effort around known insecticidal compounds. Many of these compounds showed excellent activity against key sap‐feeding insect pests in insecticidal bioassays. While analogs bearing monocyclic thiophene head groups showed activity against Myzus persicae (green peach aphid), analogs with diarylethane head groups were active against both M. persicae and Bemisia tabaci (sweetpotato whitefly). Despite compelling activity in these laboratory tests, these compounds showed diminished activity when applied to host plants via tracksprayer.CONCLUSIONSThe initial hypothesis that structural modification of molecules reported to have insecticidal activity would yield novel compounds that also exhibit insecticidal activity was validated. Despite excellent activity in laboratory bioassays, these new compounds failed to show compelling activity in more demanding tracksprayer tests. © 2016 Society of Chemical Industry