研發新型RAD 51 與 NF-kB抑制劑：IBR2衍生物以及氨基呋喃鍵結苯并咪唑與合成磷酰吡唑鍵結苯并咪唑

Abstract

本篇論文運用多分子反應，合成不同主架構的有機小分子，並將之投入抗癌標靶藥物之活性篩選，以期找出具有高抑制效率的藥物先導。 本篇論文可以分為三個部分： 第一部分是改良現有IBR2的合成方法，將原本二個合成步驟的反應流程改善成一鍋化反應，並將反應時間從原先的20小時縮短到30分鐘，藉由IBR2不同位置取代基的衍生化，得到一系列的IBR2衍生物分子庫，最後對這些化合物進行生物活性之探討。 第二部分是利用2-氰甲基苯并咪唑化合物與2-溴乙酮類化合物進行環化反應，合成具有呋喃 (furan) 結構的分子庫，以及進行結構與活性之探討 (SAR)。 第三部分是利用2-氰甲基苯并咪唑化合物為起始物，與醛類化合物、BOR試劑，經由縮合反應、環化反應，合成具有吡唑 (pyrazole) 結構的分子庫；並且利用一鍋化反應以減少時間與資源的浪費。

In this thesis, we used multicomponent reactions for synthesis of different main architecture of small organic molecules and did the biological screening for anticancer activity, in order to identify the high inhibition of drug leads. This thesis can be divided into three parts: The first part reported the improvement of the synthetic approach for the assembling of IBR2 analogues. The original two steps synthetic route was improved to one pot tandem reaction and the reaction time was reduced to 30 minutes from 20 hours. Based on this efficient synthetic approach, a series of IBR2 derivatives were prepared and these IBR2 analogues were subjected to biological screening. The second part informed that the used of 2-cyanomethylbenzimidazole and 2-bromoacetophenone for cyclization reaction to synthesis the molecular library which conformation has the furan structure as well as studied the structure-activity relationship. The third part used 2-cyanomethylbenzimidazole as a starting material through condensation reaction and cyclization reaction with aldehyde and Bestmann-Ohira reagent for synthesis the molecular library which conformation has the pyrazole structure.