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Cyclooctatetraene: A Bioactive Cubane Paradigm Complement |
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| Authors: | Dr Hui Xing Dr Sevan D Houston Xuejie Chen Dr Sussan Ghassabian Tyler Fahrenhorst-Jones Dr Andy Kuo Cody-Ellen P Murray Kyna-Anne Conn Kara N Jaeschke Da-Yun Jin Dr Cielo Pasay Prof Paul V Bernhardt Dr Jed M Burns Dr John Tsanaktsidis Dr G Paul Savage Dr Glen M Boyle Prof James J De Voss Prof James McCarthy Prof Gimme H Walter Prof Thomas H J Burne Prof Maree T Smith Prof Jian-Ke Tie Prof Craig M Williams |
| Institution: | 1. School of Chemistry and Molecular Biosciences, University of Queensland (UQ), Brisbane, 4072 Queensland (QLD, Australia
These authors contributed equally to this work.;2. School of Chemistry and Molecular Biosciences, University of Queensland (UQ), Brisbane, 4072 Queensland (QLD, Australia;3. Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599 USA;4. Centre for Integrated Preclinical Drug Development, University of Queensland (UQ), Australia;5. School of Biological Sciences, University of Queensland (UQ), Australia;6. Queensland Brain Institute, University of Queensland (UQ), Australia;7. QIMR Berghofer Medical Research Institute, PO Royal Brisbane Hospital, Brisbane, 4029, QLD Australia;8. CISRO Manufacturing, Ian Wark Laboratory, Melbourne, 3168 Victoria (VIC, Australia |
| Abstract: | Cubane was recently validated as a phenyl ring (bio)isostere, but highly strained caged carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between the two systems for enhanced bioactive molecule discovery. |
| Keywords: | agrochemicals bioisostere cubanes cyclooctatetraenes pharmaceuticals |