Macrocyclic natural products and their derivatives are a valuable source for biologically active crop protection products and have had significant impact on the development of conventional agrochemicals. However, they can be challenging starting points for lead-generation efforts because of their size and structural complexity. Using molecular modelling and electrostatic analysis, alternative bicyclic isosteres were identified as replacements for the anti-fungal 9-membered macrocycle UK-2A. By applying a structure-based conformational approach, a series of heterocyclic replacements were derivatised to deliver promising fungicidal activity, and scaffold bioisosteres were further diversified to investigate structure-activity relationships.

Scaffold hopping and bioisosteric approaches as alternatives to macrocyclic picolinamides

ACS Fall 2021

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