Sulfonylamidine‐substituted derivatives of avibactam: Synthesis and antibacterial activity

Abstract

AbstractAvibactam is a clinically approved non‐β‐lactam based β‐lactamase inhibitor. Derivatization of this scaffold with improved inhibition profile is the demand of the day to cope with the future challenges. We successfully synthesized new derivatives of avibactam containing sulfonylamidine moieties at C2 position of the diazabicyclooctane ring. We tested in vitro antibacterial activities of newly synthesized compounds against 10 bacterial strains expressing variable β‐lactamases. All compounds did not exhibit antimicrobial profile when assayed individually; however, all compounds minimized the MIC value of the imipenem in combination. Compound 5l proved most potent against all 10 bacterial strains, and showed improved inhibition against six bacterial strains as compared with the control inhibitor, relebactam. The compound 5l may be a lead hit for future development.