Evaluation of WO2012177707 and WO2012097269: Vertex's phosphate prodrugs of gyrase and topoisomerase antibacterial agents.
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.
Trius Therapeutics, 6310 Nancy Ridge Dr, San Diego, CA 92121, USA. jfinn@triusrx.com
John
J
Finn
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D027081:DNA Gyrase / Q000187:drug effects / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D010330:Patents as Topic; D010710:Phosphates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs; D012995:Solubility; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D010710:Phosphates; D011355:Prodrugs; D059005:Topoisomerase II Inhibitors; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase