General access to cubanes as benzene bioisosteres.

ABSTRACT: The replacement of benzene rings with sp³-hybridized bioisosteres in drug candidates generally improves pharmacokinetic properties while retaining biological activity^1-5. Rigid, strained frameworks such as bicyclo[1.1.1]pentane and cubane are particularly well suited as the ring strain imparts high bond strength and thus metabolic stability on their C-H bonds. Cubane is the ideal bioisostere as it provides the closest geometric match to benzene^6,7. At present, however, all cubanes in drug design, like almost all benzene bioisosteres, act solely as substitutes for mono- or para-substituted benzene rings^1-7. This is owing to the difficulty of accessing 1,3- and 1,2-disubstituted cubane precursors. The adoption of cubane in drug design has been furt

SUBMITTER: Wiesenfeldt MP 

PROVIDER: S-EPMC10680098 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature