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-4 H-benzo1,4oxazin-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.