Infection Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA
Abstract:
Optimization of adenosine analog inhibitors of bacterial NAD+-dependent DNA ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and Staphylococcus aureus was improved by modification of the 2-position substituent on the adenine ring and 3′- and 5′-substituents on the ribose. Compounds with log D values 1.5-2.5 maximized potency and maintained drug-like physical properties.