[2]-Ladderanes as isosteres for meta-substituted aromatic rings and rigidified cyclohexanes.
Rachel C EpplinShashwati PaulLoïc HerterChristophe SalomeErin N HancockJay F LarrowErich W BaumDavid R DunstanCarol Ginsburg-MoraffThomas C FessardM Kevin BrownPublished in: Nature communications (2022)
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.