Cyclooctatetraene: A Bioactive Cubane Paradigm Complement.
Hui XingSevan D HoustonXuejie ChenSussan GhassabianTyler Fahrenhorst-JonesAndy KuoCody-Ellen P MurrayKyna-Anne ConnKara N JaeschkeDa-Yun JinCielo PasayPaul V BernhardtJed M BurnsJohn TsanaktsidisG Paul SavageGlen M BoyleJames J De VossJames McCarthyGimme H WalterThomas H J BurneMaree T SmithJian-Ke TieCraig M WilliamsPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2019)
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.
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