CombiChem at Bayer CropScience: What we have learned, exemplified by recent chemistries

At Bayer CropScience combinatorial chemistry has been used to significantly increase and diversify the compound collection for high throughput in vitro and in vivo screening. Quality aspects were seen critical along this process, from the selection of novel chemotypes with a known biological background to the purity of the test compounds. This will be exemplified by a benzotriazole library obtained by a polymer-bound version of the Sanger reagent attached via a traceless triazene linker (T1). After identification of initial fungicidal activity a thorough analysis in all relevant internal chemical and biological databases revealed the structural requirements for 2(nd) validation libraries, increasing the success likelihood to find potential leads worth further optimization. In a second combinatorial approach peptides with an agro-relevant mode of action will be used to derive new active ingredients. Based on cyclopropylideneacetate chemistry, a structurally extremely flexible peptidomimetic system has been developed for systematic modification of biologically important peptide motifs in potentially optimized conformations. The next step will be the identification of analogues based on this structural informations.