Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
Maryne A. J. Dubois, Rosemary A. Croft, Yu‐Jie Ding, Chulho Choi, Dafydd R. Owen, James A. Bull, James J. Mousseau
Abstract
-dimethyl and carbonyl groups has been demonstrated to often improve chemical properties of target molecules for drug discovery purposes. The investigation of the properties of 3,3-diaryloxetanes, particularly of interest as a benzophenone replacement, remains largely unexplored. With recent synthetic advances in accessing this motif we studied the effects of 3,3-diaryloxetanes on the physicochemical properties of 'drug-like' molecules. Here, we describe our efforts in the design and synthesis of a range of drug-like compounds for matched molecular pair analysis to investigate the viability of the 3,3-diaryloxetane motif as a replacement group in drug discovery. We conclude that the properties of the diaryloxetanes and ketones are similar, and generally superior to related alkyl linkers, and that diaryloxetanes provide a potentially useful new design element.