Morpholino-substituted pyridopyrimidine,
quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-
kinase, an
enzyme that regulates
platelet-adhesion processes. As a consequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. The compounds claimed are represented by formula (I), (II) and (III). PI 3-
kinase generates 3-phosphorylated PI second messengers which stimulate
platelet adhesion under blood-flow conditions. Because
platelet adhesion is a necessary step in the formation of a
thrombus, inhibition by these compounds of PI 3-
kinase under such conditions inhibits or prevents
thrombus formation. The compounds are useful in treating PI 3-kinase-dependent conditions including cardiovascular diseases such as coronary
artery occlusion,
stroke, acute coronary syndrome, acute
myocardial infarction, vascular
restenosis, atherosclerosis, and
unstable angina; respiratory diseases such as
asthma, chronic
obstructive pulmonary diseases (
COPD), and
bronchitis; inflammatory disorders; neoplasms including cancers such as
glioma,
prostate cancer,
small cell lung cancer, and
breast cancer, and diseases linked to disordered
white blood cell function, such as autoimmune and inflammatory diseases.