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Phenyl acetate derivatives, fluorine-substituted on the phenyl group, as rapid recovery hypnotic agents with reflex
Heng Zhang1, Xiangqing Xu2, Yin Chen2
1Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Abstract:
We report the synthesis of novel, potentially hypnotic fluorine-substituted phenyl acetate derivatives. We describe the structure-activity relationship that led us to the promising derivative: ethyl 2-(4-(2-(diethylamino)-2-oxoethoxy)-5-ethoxy-2-fluorophenyl) acetate (55). The unique pharmacological features of compound 55 are its relatively high affinity for the GABAA receptor, together with a unique affinity for the NMDA receptor, different to propanidid and AZD3043. In animal models, compound 55 showed stronger hypnotic potency and longer duration of LORR than propanidid and AZD3043, but also maintained a rapid recovery time to walking and behavioral recovery. In particular, compound 55 displayed reflex depression during infusion.
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