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. ##STR00001##