6965-44-2Relevant articles and documents
Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
Bull, James A.,Choi, Chulho,Croft, Rosemary A.,Ding, Yujie,Dubois, Maryne A. J.,Mousseau, James J.,Owen, Dafydd R.
supporting information, p. 2045 - 2052 (2022/02/23)
Oxetanes have received increasing interest in medicinal chemistry as attractive polar and low molecular weight motifs. The application of oxetanes as replacements for methylene, methyl,gem-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.
