申请人:AstraZeneca AB
公开号:EP1857443A2
公开(公告)日:2007-11-21
Morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-kinase, an enzyme that regulates platelet-adhesion processes. As a cansequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. 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 restenasis, 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.
吗啉基取代的吡啶嘧啶、喹诺酮和苯并吡喃酮衍生物可抑制磷脂酰肌醇(PI)3-激酶,这是一种调节血小板粘附过程的酶。因此,这些化合物具有抗血栓活性和其他药物特性。PI 3-kinase 生成 3 磷化 PI 第二信使,在血液流动条件下刺激血小板粘附。由于血小板粘附是血栓形成的必要步骤,因此在这种条件下,这些化合物对 PI 3- 激酶的抑制可抑制或防止血栓形成。这些化合物可用于治疗 PI 3- 激酶依赖性疾病,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型心绞痛;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有关的疾病,如自身免疫性疾病和炎症性疾病。