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Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis

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 fo...

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Autores principales: Dubois, Maryne A. J., Croft, Rosemary A., Ding, Yujie, Choi, Chulho, Owen, Dafydd R., Bull, James A., Mousseau, James J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672821/
https://www.ncbi.nlm.nih.gov/pubmed/35024613
http://dx.doi.org/10.1039/d1md00248a
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author Dubois, Maryne A. J.
Croft, Rosemary A.
Ding, Yujie
Choi, Chulho
Owen, Dafydd R.
Bull, James A.
Mousseau, James J.
author_facet Dubois, Maryne A. J.
Croft, Rosemary A.
Ding, Yujie
Choi, Chulho
Owen, Dafydd R.
Bull, James A.
Mousseau, James J.
author_sort Dubois, Maryne A. J.
collection PubMed
description 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.
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spelling pubmed-86728212022-01-11 Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis Dubois, Maryne A. J. Croft, Rosemary A. Ding, Yujie Choi, Chulho Owen, Dafydd R. Bull, James A. Mousseau, James J. RSC Med Chem Chemistry 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. RSC 2021-10-06 /pmc/articles/PMC8672821/ /pubmed/35024613 http://dx.doi.org/10.1039/d1md00248a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Dubois, Maryne A. J.
Croft, Rosemary A.
Ding, Yujie
Choi, Chulho
Owen, Dafydd R.
Bull, James A.
Mousseau, James J.
Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
title Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
title_full Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
title_fullStr Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
title_full_unstemmed Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
title_short Investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
title_sort investigating 3,3-diaryloxetanes as potential bioisosteres through matched molecular pair analysis
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672821/
https://www.ncbi.nlm.nih.gov/pubmed/35024613
http://dx.doi.org/10.1039/d1md00248a
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