[2]-Ladderanes as isosteres for meta-substituted aromatic rings and rigidified cyclohexanes.

Epplin, Rachel C; Paul, Shashwati; Herter, Loïc; Salome, Christophe; Hancock, Erin N; Larrow, Jay F; Baum, Erich W; Dunstan, David R et al. · Nat Commun · 2022

basic_science · Level V

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Abstract

Aromatic ring isosteres and rigidified saturated hydrocarbons are important motifs to enable drug discovery. Herein we disclose [2]-ladderanes as a class of meta-substituted aromatic ring isosteres and rigidified cyclohexanes. A straightforward synthesis of the building blocks is presented along with representative derivatization. Preliminary studies reveal that the [2]-ladderanes offer similar metabolic and physicochemical properties thus establishing this class of molecules as interesting motifs.

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