臺灣博碩士論文加值系統

本篇論文主旨在於研究4-(經取代苯胺基)quinazoline衍生物合成之
探討，根據報導此化合物於C4~C8位置上以不同的取代基進行取代，所得
衍生物可作為酪胺酸激素抑制劑。因此本合成共分為三個步驟：第一步首
先以monochloroanthranilic acid及dichloroanthranilic acid為起始物
，分別與formamide於高溫迴流系統下進行環合反應，可得單及雙氯取
代4-hydroxy-quinazoline產物(1a,40%；1b,91%；1c,86%、1d,82%)，第
二步將化合物1用phosphorus oxychloride(POCl3)及phosphorus
pentachloride(PCl5)進行鹵化反應，可形成4,5-2Cquinazoline(2a,70%)
；4,6-2Cl-quinazoline(2b,83%)；4,7-2Cl-quinazoline(2c,70%)
；4,6,8-3Cl-quinazoline(2d,30%)，第三步則將化合物2與3-乙炔苯胺於
異丙醇迴流下反應，最後得到標的產物monochloro-quinazolin-4-yl-3-
ethynylphenylamine.HCl及dichloro-quinazolin-4-yl-3-
ethynylphenyl-amine.HCl (3a,15%；3b,60%；3c,40%；3d,40%)。合成之
標的產物 與人類鼻咽癌、肝癌、子宮頸癌、結腸癌細胞進行體外細胞毒
性試驗,初步結果顯示部分衍生物確實具有抗癌的生物活性存在.

The objective of this thesis is to investigate the synthesis of
4-(substitutedphenylamino)quinazoline derivatives. Because the
C4-C8 sites of the compound with different substituents are able
to be used as tyrosine kinase inhibitors.In the study,it consist
of three synthetic processes.Firstly,the starting material,
monochloroanthranilic acid and dichloroanthranilic acid reacted
with formamide in high temperature and refluxed to give mono-
and di-chloro substituted 4-hydroxy-quinazoline products
(1a,40%;1b,91%;1c,86%;1d,82%).Secondly,the mono- and di-chloro-
substituted-4-hydroxy-quinazoline products were carried out a
chlorination reaction with phosphorus oxychloride(POCl3)and
phosphorus pentachloride(PCl5)to form 4,5-2Cl-quinazoline(2
a,70%);4,6-2Cl-quinazoline(2b,83%);4,7-2Cl-quinazoline(2
c,70%);4,6,8-3Cl-quinazoline(2d,30%).Thirdly,the chlorination
products reacted with 3-ethynylphenylamine in isopropyl alcohol
under refluxing.Finally,the target compounds monochloro-
quinazolin-4-yl-3-ethynylphenyl-amine.HCl and dichloro-
quinazolin-4-yl-3-ethynylphenyl-amine.HCl(3a,15%;3b,60%;3c,40%;3
d,40%)were obtained.The bilogical bioassay of the target
compounds were carried out with cyto toxicity test of cell
lines,such as:human nasalpharyngeal carcinoma(KB);human
hepatoma(HEPT-3B);human cerix carcinoma(HELA);human colon
carcinoma(COLO-205).The data of the results showed that parks of
the derivatives possess antitumor biological acitivity.