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Design, Synthesis, and Evaluation of a Series of Novel Benzocyclobutene Derivatives as General Anesthetics

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posted on 21.04.2017, 00:00 by Chen Zhang, Fangqiong Li, Yan Yu, Anbang Huang, Ping He, Ming Lei, Jianmin Wang, Longbin Huang, Zhenhong Liu, Jianyu Liu, Yonggang Wei
In the present work, a series of structurally novel benzocyclobutene derivatives were identified as general anesthetics through the loss of righting reflex (LORR) experiment on mice. Our initial efforts found compound 1a with a fused four-membered ring on the 2,3-position of the phenol ring could significantly improve the safety profile. Further SAR study revealed that small hydrogen bond acceptor (HBA) groups are optimal for good ED50 along with much broader therapeutic windows, such as compounds 16b and 17. Present work demonstrates the superiority of this novel benzocyclobutene scaffold.