A combinatorial synthesis approach for agrochemical lead discovery

Combinatorial chemistry was used as a tool for delivering 10 diverse libraries as one approach for increasing the number of compounds with desirable properties entering in vivo HTS screens. The libraries consisted of polar, weak acids -materials whose physical properties are known to confer phloem mobility, a desirable attribute for reliable herbicidal activity. Part of this effort was focused towards the preparation of a series of libraries based on pyridine carboxylic acids. Details of preparation of one such library of 5,6-disubstituted nicotinic acids are described. The screening inputs prepared using this targeted, attribute-driven combinatorial chemistry approach provided a nearly 5-fold higher pass rate than randomly selected inputs. Hits from three of these libraries showed sufficient levels of activity in higher level testing to warrant further synthesis.