Researchers develop new chemical method to improve drug discovery

Moffitt Cancer Center researchers have developed a new reagent that improves the precision of drug synthesis. The innovative method, published in Nature Communicationspresents a novel sulfur fluoride exchange (SuFEx) reagent that enables highly controlled production of crucial sulfur-based molecules, including sulfinamides, sulfonimidamides and sulfoximines.

These compounds are essential in the pharmaceutical industry, but they are difficult to synthesize with the required stereochemical precision. The innovative t-BuSF reagent uses strain-releasing reactivity to achieve a previously unattainable level of efficiency and selectivity, paving the way for more efficient drug development and broader applications in medical research.

“Sulfur-based compounds, including those developed using the new methods, are known to have favorable physicochemical properties that make them ideal candidates for drug development,” said Justin M. Lopchuk, Ph.D., senior author and associate member of Moffitt’s Department of Drug Discovery. “The ability to rapidly synthesize these compounds and the stereochemical control opens new possibilities for designing targeted therapies that fight cancer cells more effectively while minimizing side effects.”

By exploiting the unique properties of the t-BuSF reagent, the researchers were able to explore previously inaccessible chemical spaces within the sulfur family, particularly in the S(IV) and S(VI) oxidation states. This advance has enabled the creation of more than 70 new chemical compounds, many of which have immediate applications in medicinal chemistry and in the development of new pharmaceutical agents.

Lopchuk adds that this research has already been used to significantly improve the scalable synthesis of DFV890, an investigational Novartis compound currently in clinical trials at Moffitt and other sites for myeloid diseases.