New chemical method developed to improve drug discovery

A new chemical method has been developed that improves drug discovery by enabling the precise synthesis of complex sulfur compounds, paving the way for advanced drug development.

The method introduces a new sulfur fluoride exchange reagent (SuFEx) that enables highly controlled production of important sulfur-based molecules, including sulfinamides, sulfonimidamides, and sulfoximines.

These compounds are indispensable in the pharmaceutical industry, but their synthesis with the required stereochemical fidelity is challenging.

The innovative reagent t-BuSF utilizes stress release reactivity to achieve unprecedented levels of efficiency and selectivity, paving the way for more effective 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., lead author and associate member of the Department of Drug Discovery at the Moffitt Cancer Center.

“The ability to rapidly synthesize these compounds and ensure stereochemical control opens new opportunities for the development of targeted therapies that more effectively fight cancer cells while minimizing side effects.”

By exploiting the unique properties of the t-BuSF reagent, the researchers were able to explore previously inaccessible chemical regions within the sulfur family, particularly in the S(IV) and S(VI) oxidation states.

This progress has led to the creation of over 70 new chemical compounds, many of which have immediate applications in medicinal chemistry and the development of new pharmaceutical active ingredients.

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

This study was supported by the National Institutes of Health, conducted by researchers at the Moffitt Cancer Center, and published in Nature communication.