title: Synthesis and c-Src inhibitory activity of imidazo[1,5-a]pyrazine derivatives as an agent for treatment of acute ischemic stroke.
abstract: We synthesized and evaluated a series of C-5 substituted imidazo[1,5-a]pyrazine derivatives to identify potent c-Src inhibitors as potential therapeutic agents for acute ischemic stroke. Among these compounds, compound 14c.HCl demonstrated remarkable central nervous system (CNS) penetration and significant neuroprotective efficacy in vivo in rat models.
authors.affiliation: Central Research Laboratory, Kissei Pharmaceutical Company Ltd, 4365-1, Azumino-city, Nagano 399-8304, Japan. harunobu_makaiyama@pharm.kissei.co.jp
authors.forename: Harunobu
authors.initials: H
authors.lastname: Mukaiyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nishimura
authors.forename: Satoko
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Ozawa
authors.forename: Noboru
authors.initials: N
authors.lastname: Kamada
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Oonota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kusama
mesh_terms: D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D018696:Neuroprotective Agents / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013055:Spectrophotometry, Infrared; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D011719:Pyrazines; C517813:imidazo(1,5-a)pyrazine; D019061:src-Family Kinases