Synthesis and c-Src inhibitory activity of imidazo[1,5-a]pyrazine derivatives as an agent for treatment of acute ischemic stroke.
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.
Mukaiyama
Harunobu
H
Central Research Laboratory, Kissei Pharmaceutical Company Ltd, 4365-1, Azumino-city, Nagano 399-8304, Japan. harunobu_makaiyama@pharm.kissei.co.jp
Nishimura
Toshihiro
T
Kobayashi
Satoko
S
Ozawa
Tomonaga
T
Kamada
Noboru
N
Komatsu
Yoshimitsu
Y
Kikuchi
Shinji
S
Oonota
Hideki
H
Kusama
Hiroshi
H
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*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D011719:Pyrazines; C517813:imidazo(1,5-a)pyrazine; D019061:src-Family Kinases