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

Authors: Rachel C. Epplin, Shashwati Paul, Loïc Herter, Christophe Salome, Erin N. Hancock, Jay F. Larrow, Erich W. Baum, David R. Dunstan, Carol Ginsburg-Moraff, Thomas C. Fessard, M. Kevin Brown

Published: 2022-10-13

DOI: 10.1038/s41467-022-33827-3

Source: Full article

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Abstract

AbstractAromatic 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.