928776-04-9Relevant articles and documents
Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinaseγ
Lanni Jr., Thomas B.,Greene, Keri L.,Kolz, Christine N.,Para, Kimberly S.,Visnick, Melean,Mobley, James L.,Dudley, David T.,Baginski, Theodore J.,Liimatta, Marya B.
, p. 756 - 760 (2007/10/03)
The Type 1 PI3Kinases comprise a family of enzymes, which primarily phosphorylate PIP2 to give the second messenger PIP3, a key player in many intracellular signaling processes [Science, 2002, 296, 1655; Trends Pharmacol. Sci. 2003, 24, 366]. Of the four type 1 PI3Ks, the γ-isoform, which is expressed almost exclusively in leukocytes [Curr. Biol., 1997, 7, R470], is of particular interest with respect to its role in inflammatory diseases such as rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) [Mol. Med. Today, 2000, 6, 347]. Investigation of a series of 4,6-disubstituted-4H-benzo[1,4]oxazin-3-ones has led to the identification of single-digit nanomolar inhibitors of PI3Kγ, several of which had good cell based activity and were shown to be active in vivo in an aspectic peritonitis model of inflammatory cell migration.
