本論文主旨在設計與合成吲唑化合物為北極光激酶抑制劑，期望以此發展為抗癌標靶藥物。以ATP競爭抑制劑概念為基礎進行開發，首先利用子結構(sub-structure)進行分子庫搜尋，篩選出潛力化合物74為修飾目標，利用電腦輔助片段基礎設計引入丙烯醯胺片段得到化合物50a，再以循理性藥物設計方式，於吲唑骨架五號位置引入苯磺醯胺片段發展出先導化合物74，並從電腦輔助模型瞭解其結構與北極光激酶之間的作用力，接著建構先導化合物74之結構活性關係與類藥性質的改善用以提升癌細胞株抑制活性，最後，進行多靶點激酶抑制活性與北極光激酶家族選擇性抑制活性測試探討此吲唑系列對於激酶選擇性抑制的表現。

This dissertation is concerned with the development of indazole-based derivatives as Aurora kinases inhibitors. Based on the concept of ATP competitive inhibitors, indazole skeleton was selected as a starting point. Utilizing our in-house database by sub-structure screening, hit compound 47 was identified as the initial hit which showed weak inhibition against Aurora A. Compound 50a was further synthesized by using in silico FBDD techniques and resulting in 10-fold potency improvement. Following by rational drug design, the carboxylic acid group extended from aniline at the C-3 of indazole core and phenylsulfonamide group at the C-5 of indazole core are newly identified to improve the potency as lead compound 74. SAR of lead compound 74 was constructed as well as the drug-like property was modified to enhance activity against cancer cell proliferation. Finally, kinases profiling and isoform selectivity were assayed and discussed through computer assisted docking model.

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