3-Oxabicyclo[3.1.1]heptane as an Isostere of meta-Benzene

Abstract

3-Oxabicyclo[3.1.1]heptanes were designed as saturated isosteres of meta-benzene. Crystallographic analysis revealed that these structures and meta-benzene have identical geometric properties. Replacement of the central benzene ring in the anticancer drug Sonidegib with 3-oxabicyclo[3.1.1]heptane provided a patent-free analogue with a nanomolar potency, reduced lipophilicity, and improved water solubility (>500%).