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.
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