Premium
Design, Synthesis, and Biological Evaluation of Novel CNS 7056 Derivatives as Sedatives in Rats and Rabbits
Author(s) -
Liu Yan,
Xu Xiangqing,
Xie Jianyong,
Ma Huan,
Wang Tao,
Zhang Guisen,
Li Qingeng
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12731
Subject(s) - sedative , medicine , pharmacology , ed50 , anesthetic , anesthesia , receptor
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 ED 50 , LD 50 , 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.