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.
Morpholino取代的
吡啶并[3,4-d]
吡咯啉,
喹诺酮和苯并
吡喃衍
生物抑制
磷脂酰肌醇(
PI)3-激酶,这是一种调节血小板粘附过程的酶。因此,所述化合物具有抗血栓活性以及其他制药特性。所要求的化合物由公式(I),(II)和(III)表示。
PI 3-激酶产生3-
磷酸化的
PI第二信使,在血流条件下刺激血小板粘附。由于血小板粘附是形成血栓的必要步骤,这些化合物在此类条件下抑制
PI 3-激酶抑制或预防血栓形成。这些化合物在治疗
PI 3-激酶依赖性疾病方面有用,包括心血管疾病,如冠状动脉闭塞,中风,急性冠状动脉综合征,急性心肌梗塞,血管再狭窄,动脉粥样硬化和不稳定性心绞痛;呼吸系统疾病,如哮喘,慢性阻塞性肺病(
COPD)和支气管炎;炎症性疾病;肿瘤,包括胶质瘤,前列腺癌,小细胞肺癌和乳腺癌等癌症;以及与白细胞功能紊乱相关的疾病,如自身免疫和炎症性疾病。