| 摘要: | 在我們不斷探索與開發新型的抗血小板與抗血管新生藥歷程中，曾經合成一系列indazole 類衍生物，並在這類雜環化合物中發現很多生物活性優異的物質。其中1-benzyl-3-(5』- hydroxymethyl-2』-furyl) indazole (YC-1)被証實是一種活性很強的血管新生抑制劑，具有開發潛能，可能成為治療癌症與血管新生相關疾病的藥物。在本計畫中，我們以selenolopyrazole 作為核心結構，將合成1, 3, 5-substituted selenolo [3, 2-c] pyrazole derivatives (I)及2, 3, 5-substituted selenolo [3, 2-c] pyrazole derivatives (II)等兩類衍生物。並評估這些標的化合物的抗血小板、抗心血管新生以及抗癌作用。我們預期在二年內找到數種新的先導化合物，進行這些先導化合物的優化並大量合成提供動物試驗。
In our continuing work aimed at the discovery and development of novel anti-platelet and anti-angiogenic agents, a series of indazole derivatives were synthesized, a lot of these compounds showed excellent biological activities. Among them, 1-benzyl-3-(5』-hydroxymethyl-2』-furyl) indazole (YC-1) was found to be a potent anti-angiogenesis inhibitor with the potential to become a useful agent in the treatment of human cancer and other angiogenesis-dependent diseases. In this research project, selenolopyrazole was selected as core structure, two series of 1,3,5-substituted selenolo [3,2-c] pyrazole derivatives (I) and 2,3,5-substituted selenolo [3,2-c] pyrazole derivatives (II), will be synthesized. The antiplatelet, antiangiogenesis and anticancer activities of these target compounds will be evaluated. We anticipate that the results in two-year period will lead to the identification of new lead compounds, the achievement of lead optimization and the accomplishment of large scale production of promising compounds for in vivo study. |
