1033744-45-4Relevant academic research and scientific papers
Rational design of phosphoinositide 3-kinase inhibitors that exhibit selectivity over the phosphoinositide 3-kinase isoform
Heffron, Timothy P.,Wei, Binqing,Olivero, Alan,Staben, Steven T.,Tsui, Vickie,Do, Steven,Dotson, Jennafer,Folkes, Adrian J.,Goldsmith, Paul,Goldsmith, Richard,Gunzner, Janet,Lesnick, John,Lewis, Cristina,Mathieu, Simon,Nonomiya, Jim,Shuttleworth, Stephen,Sutherlin, Daniel P.,Wan, Nan Chi,Wang, Shumei,Wiesmann, Christian,Zhu, Bing-Yan
, p. 7815 - 7833 (2012/01/05)
Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3K has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K vs PI3K selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K that is not attained with the corresponding Lys777 of PI3K. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.
PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND METHODS OF USE
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Page/Page column 199, (2008/12/06)
Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and R3 is a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. Formula (Ic) and (Id).
