In the search for novel active ingredients it appears often that due to issues related to insufficient level of activity, blocked intellectual property, too high complexity of lead compounds (e.g. natural products), unfavourable metabolic stability, not ideal physicochemical properties, adverse findings in toxicology studies etc., the scaffold of a molecule needs to be changed to give the respective chemistry class a chance to be optimized further. One of the drug discovery techniques, which might find a solution to the above described problems is scaffold hopping, the replacement of the complete framework of a molecule or a part of it by another scaffold with the intention to either improve the properties of the compound or to find similar potent compounds that exist in novel chemical space. In this regard, scaffold hopping can be interpreted as the broadest expansion of the bioisosterism concept. This lecture tries to demonstrate, how scaffold hopping approaches contributed to the successful optimization and development of agrochemicals. Tools like isosteric ring replacement, ring opening and ring closure approaches, functional group isosterism, inversion of functional groups, substituent scrambling, chain shortening, chain elongation, scaffold hopping across indications, hopping with privileged scaffolds and 1,3 nitrogen shift and cyclic imine – amide isosterism will be explained.

Scaffold hopping approaches in the agrochemical lead optimization

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.