14192-58-6Relevant articles and documents
A novel necroptosis inhibitor - Necrostatin-21 and its SAR study
Wu, Zhijie,Li, Ying,Cai, Yu,Yuan, Junying,Yuan, Chengye
, p. 4903 - 4906 (2013/09/02)
An initial structure-activity relationship study of the novel necroptosis inhibitor Nec-21 was described. Any changes of the tetracyclic scaffold were detrimental for the activity. Introduction of a substituent to 7 or 8 position (e.g., cyano or methoxy group, respectively), would increase the activity. The 7 and 8-position disubstituted compound 17b was 35-fold as potent as the lead, while EC50 reached 14 nM.
A back-to-front fragment-based drug design search strategy targeting the DFG-out pocket of protein tyrosine kinases
Iwata, Hidehisa,Oki, Hideyuki,Okada, Kengo,Takagi, Terufumi,Tawada, Michiko,Miyazaki, Yasushi,Imamura, Shinichi,Hori, Akira,Lawson, J. David,Hixon, Mark S.,Kimura, Hiroyuki,Miki, Hiroshi
, p. 342 - 346 (2012/06/18)
We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.
A pentacyclic aurora kinase inhibitor (AKI-001) with high in vivo potency and oral bioavailability
Rawson, Thomas E.,Rüth, Matthias,Blackwood, Elizabeth,Burdick, Dan,Corson, Laura,Dotson, Jenna,Drummond, Jason,Fields, Carter,Georges, Guy J.,Goller, Bernhard,Halladay, Jason,Hunsaker, Thomas,Kleinheinz, Tracy,Krell, Hans-Willi,Li, Jun,Liang, Jun,Limberg, Anja,McNutt, Angela,Moffat, John,Phillips, Gail,Ran, Yingqing,Safina, Brian,Ultsch, Mark,Walker, Leslie,Wiesmann, Christian,Zhang, Birong,Zhou, Aihe,Zhu, Bing-Yan,Rüger, Petra,Cochran, Andrea G.
scheme or table, p. 4465 - 4475 (2009/07/11)
Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead
INDOLE DERIVATIVE AND USE FOR TREATMENT OF CANCER
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Page/Page column 197, (2010/02/15)
The present invention relates to a compound represented by the formula (I’) wherein A is a benzene ring optionally having substituents, R1, R2a and R3 are each a hydrogen atom, a hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, R1 and R2a may form a ring via X, when R1 and R2a form a ring via X, R1 and R2a are each a bond or a divalent C1-5 acyclic hydrocarbon group optionally having substituents, and X is a bond, an oxygen atom, an optionally oxidized sulfur atom or an imino group optionally having a substituent, provided that R1, R2a and X are not bonds at the same time, or a salt thereof, and an agent for inhibiting kinase (phosphorylation enzyme), which contains this compound or a prodrug thereof. The compound of the present invention has an inhibitory activity against kinase such as a vascular endothelial growth factor receptor (VEGFR) and the like, and is useful as an agent for the prophylaxis or threatment of cancer and the like.
