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A new water-soluble benzodiazepine derivative, CNS 7056 (named as remimazolam), has been undergoing many reactions in recent years to provide an intravenous agent with a predictable fast-onset, short duration of action, and rapid recovery profile. Based on the structure of CNS 7056 with proven activity, seven new CNS 7056 derivatives were designed, and their sedative activities upon mouse, rats, and rabbits were examined. Sedative activities of EL -001˜007 were screened. The results indicated that the shorter the side chain at C3 position is, the higher the sedative activity is. EL -001 was chosen as the optimal compound for studies of ED50, LD50, latency to LRR and the duration of LRR, and its anesthetic activity was compared with that of CNS 7056 in rats and rabbits. Studies showed that EL -001 is a potent sedative in rodent and lagomorpha, with a short duration of action. Compared with CNS 7056, EL -001 has a shorter period of induction despite a slightly longer sedative duration and recovery time. [ABSTRACT FROM AUTHOR]

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 GABA A 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. [ABSTRACT FROM AUTHOR]