754207-57-3Relevant academic research and scientific papers
Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) as an antiinflammatory target: Discovery and in vivo activity of selective pyrazolo[1,5- a ]pyrimidine inhibitors using a focused library and structure-based optimization approach
Kosugi, Tomomi,Mitchell, Dale R.,Fujino, Aiko,Imai, Minoru,Kambe, Mika,Kobayashi, Shinji,Makino, Hiroaki,Matsueda, Yohei,Oue, Yasuhiro,Komatsu, Kanji,Imaizumi, Keiichiro,Sakai, Yuri,Sugiura, Satoshi,Takenouchi, Osami,Unoki, Gen,Yamakoshi, Yuko,Cunliffe, Vicky,Frearson, Julie,Gordon, Richard,John Harris,Kalloo-Hosein, Heidi,Le, Joelle,Patel, Gita,Simpson, Donald J.,Sherborne, Brad,Thomas, Peter S.,Suzuki, Naotaka,Takimoto-Kamimura, Midori,Kataoka, Ken-Ichiro
, p. 6700 - 6715 (2012/09/25)
A novel class of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) inhibitors was discovered through screening a kinase-focused library. A homology model of MAPKAP-K2 was generated and used to guide the initial SAR studies and to rationalize the observed selectivity over CDK2. An X-ray crystal structure of a compound from the active series bound to crystalline MAPKAP-K2 confirmed the predicted binding mode. This has enabled the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives showing good in vitro cellular potency as anti-TNF-α agents and in vivo efficacy in a mouse model of endotoxin shock.
