A Miniaturized Chemical High Throughput Experimentation Plate to Enable Late-Stage Oxidation Screening and Scale-up

Chemical methods for Late-Stage Oxidation (LSO) of advanced and complex molecules remain a highly relevant topic, with new and improved methods being reported annually. Despite the growing number of methodologies, the scope and limitations of these methods in bioactive molecules is largely unknown. We have designed a High-Throughput Experimentation (HTE) plate based on validated LSO methods, capable of screening compounds using only a few milligrams, to enhance our Late-Stage Functionalization (LSF) platform. Various projects at AbbVie have benefited from this plate, generating essential data for programs and creating new analogs for comprehensive Structure-Activity Relationship (SAR) analysis. We demonstrated the transformative capabilities of this approach by screening nine well-known drugs and analyzed the oxidized derivatives. This report highlights how this overlooked transformation can be an effective synthetic tool for medicinal chemistry.