7ti2

Publication Abstract from PubMed

Early efforts to broaden the spectrum and potency of cyclic boronic acid beta-lactamase inhibitor vaborbactam included a series of 7-membered ring boronates. Exploration of stereoisomers and incorporation of heteroatoms allowed identification of the all-carbon cyclic boronate with substituents trans as the preferred core structure, showing inhibition of Class A and C enzymes. Crystal structures of one analog bound to important beta-lactamase enzymes were obtained. When isolated under acidic conditions, these compounds spontaneously formed a neutral cyclic anhydride (intramolecular prodrug) which was shown to have much-improved oral bioavailability (52-69%) compared to the ring-opened carboxylate salt (9%).

Broad-spectrum cyclic boronate beta-lactamase inhibitors featuring an intramolecular prodrug for oral bioavailability.,Raja Reddy K, Totrov M, Lomovskaya O, Griffith DC, Tarazi Z, Clifton MC, Hecker SJ Bioorg Med Chem. 2022 May 15;62:116722. doi: 10.1016/j.bmc.2022.116722. Epub 2022, Mar 23. PMID:35358864^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.