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.