Medicinal Chemistry Core

SUMMARY The Medicinal Chemistry Core (MCC) will provide synthetic and medicinal chemistry, cheminformatics, and structure-based design resources complementary to those existing within the respective project teams. It will integrate tightly with the other Cores. The MCC resource will distinguish itself by relying on extensive pharmaceutical medicinal chemistry experience in antibacterials melded with academic strengths in drug discovery and development. Critically, the MCC staff leadership has demonstrated an ability to produce drug candidates by evolving small molecules to address a wide range of problems encountered during the lead optimization process. This experience will be essential to: Project 1) the lead optimization of novel rifamycins to reach the desired product profile for Mycobacterium abscessus treatment, Project 2) the lead optimization of an indazole sulfonamide for the treatment of Mycobacterium avium infection, Project 4) the delivery of a novel tarocin:β-lactam combination product suitable for the treatment of Staphylococcus aureus and Staphylococcus epidermidis infections, and Project 5) the delivery of an arylmyxopyronin for drug-resistant bacterial infections. These projects necessitate experience with a diverse range of chemistries as found in the description of the MCC member backgrounds. Overall, the spectrum and depth of the MCC staff's industrial and academic background will prove critical to their ability to optimize leads within the individual projects to molecules with significant potential for positively impacting the antibacterial clinical landscape to address the global health crisis.