There is a clear need for safe and effective therapies to treat onychomycosis that affects up to 14% of the general U.S. population indicating that up to 42 million Americans may have this disease. A structural diversification strategy was employed in lead identification stage for our antifungal program. As shown in Figure 1, in order to reduce lipophilicity of CBE compounds, we replaced the northern phenyl ring with a hydroxy group giving cyclic boronic acids (CBOs). AN-2679 was identified as a lead that has better water solubility and hydrophilicity in comparison to CBE-1 and also exhibits good antifungal activity. Lead optimization investigation of CBO series starting from AN-2679 led to the discovery of 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole (AN-2690), which demonstrates broad-spectrum antifungal activity with minimum inhibitory concentration (MIC) values ranging from 0.25 - 1.0 µg/mL against T. rubrum, T. mentagrophytes, C. albicans, C. neoformans and A. fumigatus with or without keratin. AN-2690 is currently in clinical trials for the topical treatment of onychomycosis.