Spiro[3.3]heptane as a Saturated Benzene Bioisostere

Abstract

The spiro[3.3]heptane core, with the non-coplanar exit vectors, was shown to be a saturated benzene bioisostere. This scaffold was incorporated into the anticancer drug sonidegib (instead of the meta-benzene), the anticancer drug vorinostat (instead of the phenyl ring), and the anesthetic drug benzocaine (instead of the para-benzene). The patent-free saturated analogs obtained showed a high potency in the corresponding biological assays.

Keywords: Bioisostere; Cyclobutane; Medicinal Chemistry; Spiro[3.3]Heptane; Spirocycles.