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.
| Original language | English |
|---|---|
| Pages (from-to) | 2729-2734 |
| Number of pages | 6 |
| Journal | Chemistry - A European Journal |
| Volume | 25 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 21 Feb 2019 |
| Externally published | Yes |
Keywords
- agrochemicals
- bioisostere
- cubanes
- cyclooctatetraenes
- pharmaceuticals
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In: Chemistry - A European Journal, Vol. 25, No. 11, 21.02.2019, p. 2729-2734.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Cyclooctatetraene
T2 - A Bioactive Cubane Paradigm Complement
AU - Xing, Hui
AU - Houston, Sevan D.
AU - Chen, Xuejie
AU - Ghassabian, Sussan
AU - Fahrenhorst-Jones, Tyler
AU - Kuo, Andy
AU - Murray, Cody Ellen P.
AU - Conn, Kyna-Anne
AU - Jaeschke, Kara N.
AU - Jin, Da Yun
AU - Pasay, Cielo
AU - Bernhardt, Paul V.
AU - Burns, Jed M.
AU - Tsanaktsidis, John
AU - Savage, G. Paul
AU - Boyle, Glen M.
AU - De Voss, James J.
AU - McCarthy, James
AU - Walter, Gimme H.
AU - Burne, Thomas H.J.
AU - Smith, Maree T.
AU - Tie, Jian Ke
AU - Williams, Craig M.
N1 - Funding Information: The authors thank The University of Queensland (UQ), University of North Carolina at Chapel Hill, the QIMR Berghofer Medical Research Institute, the Department of Agriculture and Water Resources (CT-06), and the CSIRO (Melbourne) for financial support; S.G. and A.K. were supported financially by Therapeutic Innovation Australia (TIA), and TIA is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program. CIPDD research infrastructure was purchased using investment funds from the Queensland Government Smart State Research Facilities Fund as well as from TIA. The Australian Research Council for a Future Fellowship award (grant number: FT110100851) to C.M.W. is also gratefully acknowledged, in addition, to the National Health and Medical Research Council of Australia (NHMRC) and National Heart, Lung, and Blood Institute, National Institutes of Health, USA (HL131690 to J.K.T. and D.W.S.). S.D.H. gratefully acknowledges the Northcote Trust and Britain–Australia Society for their award of the Northcote Graduate Scholarship. J.M.B. is indebted to The University of Queensland Research Computing Centre, the Queensland Cyber Infrastructure Foundation (QCIF) and the National Computational Infrastructure (NCI, supported by the Australian Government) for access to supercomputing resources. We thank Prof. Bryan Fry (School of Biological Sciences, UQ), Prof. Jenny Martin (University of Newcastle) and Ms. Pauline Ko (Queensland Brain Institute, UQ) for valuable discussions. Dr. Kate Mounsey, from the University of Sunshine Coast, is thanked for facilitating access to pig mites at QASP-UQ, Gatton, and providing help with mite bioassays for the scabies study. Finally, we thank the reviewer for drawing our attention to ref. [37]. Funding Information: The authors thank The University of Queensland (UQ), University of North Carolina at Chapel Hill, the QIMR Berghofer Medical Research Institute, the Department of Agriculture and Water Resources (CT-06), and the CSIRO (Melbourne) for financial support; S.G. and A.K. were supported financially by Therapeutic Innovation Australia (TIA), and TIA is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program. CIPDD research infrastructure was purchased using investment funds from the Queensland Government Smart State Research Facilities Fund as well as from TIA. The Australian Research Council for a Future Fellowship award (grant number: FT110100851) to C.M.W. is also gratefully acknowledged, in addition, to the National Health and Medical Research Council of Australia (NHMRC) and National Heart, Lung, and Blood Institute, National Institutes of Health, USA (HL131690 to J.K.T. and D.W.S.). S.D.H. gratefully acknowledges the Northcote Trust and Britain?Australia Society for their award of the Northcote Graduate Scholarship. J.M.B. is indebted to The University of Queensland Research Computing Centre, the Queensland Cyber Infrastructure Foundation (QCIF) and the National Computational Infrastructure (NCI, supported by the Australian Government) for access to supercomputing resources. We thank Prof. Bryan Fry (School of Biological Sciences, UQ), Prof. Jenny Martin (University of Newcastle) and Ms. Pauline Ko (Queensland Brain Institute, UQ) for valuable discussions. Dr. Kate Mounsey, from the University of Sunshine Coast, is thanked for facilitating access to pig mites at QASP-UQ, Gatton, and providing help with mite bioassays for the scabies study. Finally, we thank the reviewer for drawing our attention to ref. [37]. Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/2/21
Y1 - 2019/2/21
N2 - 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.
AB - 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.
KW - agrochemicals
KW - bioisostere
KW - cubanes
KW - cyclooctatetraenes
KW - pharmaceuticals
UR - http://www.scopus.com/inward/record.url?scp=85060689662&partnerID=8YFLogxK
U2 - 10.1002/chem.201806277
DO - 10.1002/chem.201806277
M3 - Article
C2 - 30681236
AN - SCOPUS:85060689662
SN - 0947-6539
VL - 25
SP - 2729
EP - 2734
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 11
ER -