3‐Oxabicyclo[3.1.1]heptane as an Isostere of <i>meta</i> ‐Benzene

D Dmitry Dibchak (Enamine Ltd. Winston Churchill st. 78 Kyiv 02094 Ukraine) P Pavel K. Mykhailiuk (Enamine Ltd, Winston Churchill St. 78, 02094 Kyiv, Ukraine)

Abstract

Abstract 3‐Oxabicyclo[3.1.1]heptanes were designed as saturated isosteres of meta ‐benzene. Crystallographic analysis revealed that these structures and  meta ‐benzene have identical geometric properties. Replacement of the central benzene ring in the anticancer drug Sonidegib with 3‐oxabicyclo[3.1.1]heptane provided a patent‐free analogue with a nanomolar potency, reduced lipophilicity, and improved water solubility (&gt;500%).

Article Details

Volume / Issue Vol. 64, Issue 25
Published June 17, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (2)

D

Dmitry Dibchak

Enamine Ltd. Winston Churchill st. 78 Kyiv 02094 Ukraine

P

Pavel K. Mykhailiuk

Enamine Ltd, Winston Churchill St. 78, 02094 Kyiv, Ukraine