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

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.