Antiparasitic dinitrile compounds for fly control in cattle

Abstract In cattle, parasitic flies such as the horn fly, Haematobia irritans, or the stable fly, Stomoxys calcitrans, are a serious nuisance for the animals and, in high populations, can cause substantial reduction in milk production, as well as significantly defer weight gain in calves. In 2012 annual losses associated with such pests were estimated to be up to 2200 million USD in the United States alone, and new effective treatments were therefore deemed highly valuable. The dinitriles were identified as a very promising class for combatting these pests, with additional potential for flea and tick control in companion animals. The molecules act as highly potent GABA-gated chloride channel blockers with IC50 values down to the single-digit nanomolar range. In addition, they possess fast knockdown activities close to state-of-the-art pyrethroids. In this chapter, the research efforts from early hit discovery to initial field testing will be described in further detail.