University of Notre Dame Du Lac

Serena Carosso

Marvin J Miller

Patricia Miller

Rui Liu

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic &#x3b2;-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized &#x3b1;-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains ofwhich have been listed by the WHO as being of critical concern worldwide.

Antibacterial monobactams

The invention provides monobactams that can be used as antibacterial agents or intermediates for the preparation of other useful compounds such as antibacterial agents.

Growing community of inventors

South Bend, IN, United States of America

Serena Carosso