Cyclooctatetraene: A Bioactive Cubane Paradigm Complement. Issue 11 (25th January 2019)

• Record Type: Journal Article
• Authors: Xing, Hui; Houston, Sevan D.; Chen, Xuejie; Ghassabian, Sussan; Fahrenhorst‐Jones, Tyler; Kuo, Andy; Murray, Cody‐Ellen P.; Conn, Kyna‐Anne; Jaeschke, Kara N.; Jin, Da‐Yun; Pasay, Cielo; Bernhardt, Paul V.; Burns, Jed M.; Tsanaktsidis, John; Savage, G. Paul; Boyle, Glen M.; De Voss, James J.; McCarthy, James; Walter, Gimme H.; Burne, Thomas H. J.; Smith, Maree T.; Tie, Jian‐Ke; Williams, Craig M.
• Is Part Of: Chemistry. Volume 25:Issue 11(2019)
• Page Start: 2729
• Page End: 2734
• Publication Date: 2019-01-25
• Subjects: agrochemicals -- bioisostere -- cubanes -- cyclooctatetraenes -- pharmaceuticals; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201806277
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : COTton on ! The potential of cyclooctatetraene (COT) as a bioactive motif was assessed using a portfolio of six pharmaceutical and agrochemical templates. The protean nature and π character of COT was found to compliment the attributes of the already established cubane (bio)isostere concept, and the facile conversion of the latter to the former inaugurate the pair as an effective tool for deployment in bioactive molecule discovery.