Enhanced Drug Discovery with Novel Sulfur Fluoride Exchange Reagent

Researchers at the Moffitt Cancer Center have created a new reagent that improves drug production precision. This novel approach, described in Nature Communications, presents a new sulfur fluoride exchange (SuFEx) reagent that enables the highly regulated manufacture of important sulfur-based compounds such as sulfinamides, sulfonimidamides, and sulfoximines.

These compounds are critical in the pharmaceutical industry, but they have proved difficult to manufacture with the necessary stereochemical precision. The novel reagent t-BuSF employs strain-release reactivity to achieve previously impossible levels of efficiency and selectivity, opening the door to more successful drug development and broader medical research applications.

Sulfur-based compounds, including those developed using the new methods, are known to have favorable physiochemical properties that make them ideal candidates for drug development.”

Justin M. Lopchuk, Ph.D., Study Lead Author and Associate Member, Drug Discovery Department, Moffitt Cancer Center

Lopchuk added, “The ability to synthesize these compounds rapidly and stereochemical control open new possibilities for designing targeted therapies that combat cancer cells more effectively while minimizing side effects.”

Using the t-BuSF reagent’s unique characteristics, researchers were able to explore hitherto inaccessible chemical space within the sulfur family, notably in the S(IV) and S(VI) oxidation states. This progress has led to the discovery of over 70 new chemical compounds, many of which have direct applications in medicinal chemistry and the development of novel pharmaceutical agents.

According to Lopchuk, this study has already significantly improved the manufacturing of DFV890, an investigational compound from Novartis that is presently undergoing clinical trials for myeloid diseases at Moffitt and other locations.