Evaluation of WO2012177707 and WO2012097269: Vertex's phosphate prodrugs of gyrase and topoisomerase antibacterial agents

Abstract

The two patent applications describe two novel compounds in the benzimidazole class of GyrB/ParE antibacterial agents and multiple phosphate prodrugs derived from these compounds. The new benzimidazole compounds have excellent antibacterial activity on Gram-positive strains. But like previous benzimidazoles, they have limited solubility and are highly protein bound. The phosphate prodrugs offer a drug substance with high aqueous solubility that should aid both intravenous and oral formulations. The potential utility of the prodrugs was demonstrated in efficacy studies.

Keywords::

• antibacterial
• DNA gyrase
• prodrugs
• topoisomerase IV