title: Multi-substituted 8-aminoimidazo[1,2-a]pyrazines by Groebke-Blackburn-Bienaymé reaction and their Hsp90 inhibitory activity.
abstract: Using a 2,3-diamino pyrazine substrate and yttrium triflate catalyst, various 2-alkyl and aryl substituted 3,8-diaminoimidazo[1,2-a]pyrazines were efficiently prepared through Groebke-Blackburn-Bienaymé MCR. In particular, a novel 2-piperonyl 3,8-diaminoimidazo[1,2-a]pyrazine structure was prepared exclusively with this new method and was found to have moderate Hsp90 inhibitory activity. A crystalline complex with N-terminus ATP domain of Hsp90 and one of the new Hsp90 inhibitors was also obtained to elucidate the origin of activity of 2-piperonyl 3,8-diaminoimidazo[1,2-a]pyrazines.
authors.affiliation: Medicinal Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P. R. China. bxiong@simm.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Hongchun
authors.initials: H
authors.lastname: Liu
authors.forename: Danyan
authors.initials: D
authors.lastname: Cao
authors.forename: Danqi
authors.initials: D
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Le
authors.initials: L
authors.lastname: Tang
authors.forename: Jianhua
authors.initials: J
authors.lastname: He
authors.forename: Yue-Lei
authors.initials: YL
authors.lastname: Chen
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.forename: Bing
authors.initials: B
authors.lastname: Xiong
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
mesh_terms: D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D011719:Pyrazines