Structure Activity Relationship (SAR) of Fluorinated and Carbamylated Beta-Lactam Derivatives

While drug-resistance exists in a wide range of clinically important microorganisms, new drug development has significantly lagged behind the need. We are directly addressing this gap in antimicrobial development by synthesizing a novel class of antimicrobials that are not inactivated by the microbial beta-lactamases. To date, we have synthesized cadres of compounds with demonstrated good activity (minimum inhibitory (MIC) and minimum bactericidal concentration, MBC, <15 ug/ml) against Mycobacterium tuberculosis (Mtb) or Moraxella catarrhalis (M.cat.). The focus of my research is to prepare a second generation of these drugs by building a library of compounds containing fluorinated derivatives. The position and multitude of the fluorine atoms in the compounds' scaffold is expected to improve overall efficacy of these compounds. In addition, preparation of compounds with differently substituted carbamyl groups has been accomplished. The Structure Activity Relationship (SAR) of these two types of compounds will be presented.