| 摘要: | Amidine 類衍生物和多環之雜環化合物擁有非常廣泛生物和藥理活性。本計畫分成三年期之研究， 主要以微波加速amidine 合成及hetero Deils-Alder 反應為研究重心，利用微波加速合成方法，合成一 系列amidines 及多環之雜環化合物做為抗癌新藥之開發。第一年將以微波方法將5-amino pyrazole 和 一系列 amide solvents 在酸性條件下，以微波方法探討合成一系列amidines 衍生物，做為未來三年 研究計畫之key intermediate 中間產物，並將合成出之一系列amidines 送測相關藥理活性。第二年計 畫將透過第一年研究成果，將最適化之amidines 當diene，與一系列dienophiles (包括: meleic anhydride, dimethyl acetylenecarboxylate DMAD, naphthalene-1,4-dione, and maleimide) 進行hetero Deils-Alder 反 應，試圖找出適合之amidines 和dienophiles 反應起始物及微波反應條件，經微波加速反應，以合成 pyridopyrrolidines 類衍生物當做先導新藥之開發。另外也嘗試以高溫高壓反應儀協助hetero Deils-Alder 反應。計畫的第三年將延伸以benzye, 2,-dehydropyridine or 2,3-quinolyne 等化合物做為 dienophiles ， 和最適化之amidines 進行微波加速hetero Deils-Alder 反應， 合成 pyrazolo[3,4-c]isoquinolines 和 Pyrazolonaphthyridines 類衍生物，做為抗癌新藥之開發。
The amidine derivatives and condensed polyazaaromatic functionality compounds exhibit a range of bioactivities in the pharmacological areas. This proposal contains the three sections projects for three years. We focus on the investigation of microwave-assisted reaction and hetero Deils-Alder reaction to synthesize a siries of amidine deriatives and the condensed polyazaaromatic ring systems. In the first year’s project, we design a microwave-assisted approach to generate the key amidine intermediates by using 5-amino pyrazole with various amide solvents in the acid condidition. As a consequence, a series of amidine compounds will be using as the key intermediate to synthesize the condensed polyazaaromatic products. The further work of second year, amidines will be treated with the dienophiles, including meleic anhydride, dimethyl acetylenecarboxylate DMAD, naphthalene-1,4-dione, and maleimide, to prepare the pyridopyrrolidines derivates. We are also investigated the the pharmacological and electroluminescent properties of pyridopyrrolidines. The high pressure and high temperature methodology would be performed to promote the reactivity of the hetero Deils-Alder reaction. In the third year, pyrazolo[3,4-c]isoquinolines and pyrazolonaphthyridines will be synthesized by amidine compound with benzye, 2,-dehydropyridine or 2,3-quinolyne in the basic condition. Novel condensed polyazaaromatic compounds will be as the anti-tumor lead products. |
