title: Design, Synthesis, and Biological Evaluation of Novel CNS 7056 Derivatives as Sedatives in Rats and Rabbits.
abstract: 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.
authors.affiliation: Division of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: R&D Department, Jiangsu Nhwa Pharmaceutical Corporation Ltd., Jiangsu, 221009, China.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Xie
authors.affiliation: Division of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.affiliation: R&D Department, Jiangsu Nhwa Pharmaceutical Corporation Ltd., Jiangsu, 221009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors.forename: Guisen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Division of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Qingeng
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C522201:remimazolam
keywords: CNS 7056 derivatives; rats and rabbits; sedation