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目 錄
中文摘要 ……………………………………………………………….... 1
英文摘要 ………………………………………………………………....2
第一章 緒論…………………………………………………………....3
第一節 抗心律不整藥物之概述…………………………………..…3
第二節 抗過敏抗發炎活性概述……………………………………..4
第三節 Substituted-2,3,4,9-tetrahydrofuro[2,3-b]qninolin-3,4-diones 類化合物之研究概況……………………………………….. 5
第四節 研究動機與目的……………………………………………..6
第二章 研究經過 …………………………………………………...9
第一節 化學合成部份 ………………………………………………..9
一.Ethyl 2-(4￠-bromoanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate ( 1 )之合成 …………………………………………………………. 10
二.6-Bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 2 )之合成 ………………………………………………………….11
三.N-substituted benzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin- 3,4-dione ( 3~12 ) 類化合物之合成 ………………………………….13
四.Ethyl 2-(3￠-bromoanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate ( 13 )之合成 ……..…………………………………………………...15
五.7-Bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 14)之合成 …………………………………………………………16
六.N-substituted benzyl -7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin- 3,4-dione ( 15~25 ) 類化合物之合成 ..……………………………….18
七.Ethyl 2-(2￠-bromoanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate ( 26 )之合成 . ……………………………………………………….20
八.8-Bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 27)之合成 …………………………………………………………21
九.N-substituted benzyl -8-bromo-2,3,4,9-tetrahydrofuro[2,3-b] quinolin-3,4-dione ( 28~38 ) 類化合物之合成 ……………………….23
十.Substituted-2,3,4,9-tetrahydrofuro[2,3-b]qninolin-3,4-diones 類化合物之物理性質數據25
第二節 藥理活性試驗結果…………………………………………….27
表七 對於Compound 48/80誘導的肥滿細胞去顆粒作用抑制試驗…………29
表八 對於fMLP誘導的嗜中性白血球去顆粒作用抑制試驗 ……………….30
表九 對於fMLP誘導的嗜中性白血球超氧自由基生成作用抑制試驗 …….31
表九 對於PMA誘導的嗜中性白血球超氧自由基生成作用抑制試驗 ……..31
第三章 結論 …………………………………………………………..32
第四章 實驗部份 ……………………………………………………33
第一節 試藥…………………………………………………………….33
第二節 儀器…………………………………………………………….35
第三節 實驗方法 ………………………………………………………36
(一) Ethyl 2-(4￠-bromoanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate ( 1 )之合成 ……..…………………………………………………36
(二) 6-Bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 2 )之合成 …..……………………………………………………37
(三) N-benzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 3 )之合成.....................................................………………...38
(四) N-o-fluorobenzyl-6-bromo -2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（4）之合成………………………………………..39
(五) N-m-fluorobenzyl-6-bromo -2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（5）之合成………………………………………..40
(六) N-p-fluorobenzyl-6-bromo -2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（6）之合成………………………………………..41
(七) N-o-methylbenzyl-6- bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（7）之合成………………………………………..42
(八) N-m-methylbenzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（8）之合成………………………………………..43
(九) N-p-methylbenzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（9）之合成………………………………………..44
(十) N-m-methoxylbenzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（10）之合成………………………………………45
(十一) N-m-chlorobenzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（11）之合成………………………………………..46
(十二) N-p-chlorobenzyl-6-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（12）之合成………………………………………..47
(十三) Ethyl 2-(3￠-bromoanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate ( 13 )之合成………………………………………………………..48
(十四) 7-Bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 14 )之合成……………………………………………………….49
(十五) N-benzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 15 )之合成…………………………………………………………………50
(十六) N-o-fluorobenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（16）之合成…………………………………51
(十七) N-m-fluorobenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（17）之合成…………………………………52
(十八) N-p-fluorobenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（18）之合成………………………………… 53
(十九) N-o-methylbenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（19）之合成…………………………………54
(二十) N-m-methylbenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（20）之合成…………………………………55
(二十一) N-p -methylbenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（21）之合成…………………………………56
(二十二) N-m-methoxybenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（22）之合成…………………………………57
(二十三) N-p-methoxybenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（23）之合成…………………………………58
(二十四) N-m-chlorobenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（24）之合成…………………………………59
(二十五) N-p-chlorobenzyl-7-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（25）之合成…………………………………60
(二十六) Ethyl 2-(2￠-bromoanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate ( 26 )之合成……………………………………………………………….61
(二十七) 8-Bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 27 )之合成……………………………………………………….62
(二十八) N-benzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione ( 28 )之合成……………………………………………………….63
(二十九) N-o-fluorobenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（29）之合成…………………………………64
(三十) N-m-fluorobenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（30）之合成…………………………………65
(三十一) N-p-fluorobenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（31）之合成…………………………………66
(三十二) N-o-methylbenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（32）之合成…………………………………67
(三十三) N-m-methylbenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（33）之合成…………………………………68
(三十四) N-p-methylbenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（34）之合成…………………………………69
(三十五) N-m-methoxybenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（35）之合成…………………………………70
(三十六) N-o-chlorobenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（36）之合成…………………………………71
(三十七) N-m-chlorobenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（37）之合成…………………………………72
(三十八) N-p-chlorobenzyl-8-bromo-2,3,4,9-tetrahydrofuro[2,3-b]- quinolin -3,4-dione（38）之合成…………………………………73
第四節 藥理實驗方法與材料…………………………………………..74
參考文獻 …………………………………..……………………………..77
附錄一（圖譜部份）
Fig 1-1 MS and IR spectra of compound 1……………………………………f001
Fig 1-2 1H-NMR and 13C-NMR spectra of compound 1……………………..f002
Fig 2-1 MS and IR spectra of compound 2…………………………………...f003
Fig 2-2 1H-NMR and 13C-NMR spectra of compound 2……………………..f004
Fig 3-1 MS and IR spectra of compound 3…………………………………...f005
Fig 3-2 1H-NMR and 13C-NMR spectra of compound 3……………………..f006
Fig 4-1 MS and IR spectra of compound 4……………………………….. …f007
Fig 4-2 1H-NMR and 13C-NMR spectra of compound 4……………………..f008
Fig 5-1 MS and IR spectra of compound 5…………………………………...f009
Fig 5-2 1H-NMR and 13C-NMR spectra of compound 5……………………..f010
Fig 6-1 MS and IR spectra of compound 6…………………………………...f011
Fig 6-2 1H-NMR and 13C-NMR spectra of compound 6……………………..f012
Fig 7-1 MS and IR spectra of compound 7………………………………...…f013
Fig 7-2 1H-NMR and 13C-NMR spectra of compound 7……………………..f014
Fig 8-1 MS and IR spectra of compound 8…………………………………...f015
Fig 8-2 1H-NMR and 13C-NMR spectra of compound 8……………………..f016
Fig 9-1 MS and IR spectra of compound 9…………………………………...f017
Fig 9-2 1H-NMR and 13C-NMR spectra of compound 9……………………..f018
Fig 10-1 MS and IR spectra of compound 10………………………………...f019
Fig 10-2 1H-NMR and 13C-NMR spectra of compound 10…………………..f020
Fig 11-1 MS and IR spectra of compound 11…………………………………f021
Fig 11-2 1H-NMR and 13C-NMR spectra of compound 11…………………..f022
Fig 12-1 MS and IR spectra of compound 12……………………………...…f023
Fig 12-2 1H-NMR and 13C-NMR spectra of compound 12……………….….f024
Fig 13-1 MS and IR spectrum of compound 13………………………………...f025
Fig 13-2 1H-NMR and 13C-NMR spectra of compound 13…………………..f026
Fig 14-1 MS and IR spectra of compound 14………………………….…. …f027
Fig 14-2 1H-NMR and 13C-NMR spectra of compound 14…………………..f028
Fig 15-1 MS and IR spectra of compound 15………………………….……..f029
Fig 15-2 1H-NMR and 13C-NMR spectra of compound 15…………………..f030
Fig 16-1 MS and IR spectra of compound 16…………………………….…..f031
Fig 16-2 1H-NMR and 13C-NMR spectra of compound 16…………………..f032
Fig 17-1 MS and IR spectra of compound 17………………………………...f033
Fig 17-2 1H-NMR and 13C-NMR spectra of compound 17…………………..f034
Fig 18-1 MS and IR spectra of compound 18………………………………...f035
Fig 18-2 1H-NMR and 13C-NMR spectra of compound 18…………………..f036
Fig 19-1 MS and IR spectra of compound 19………………………………...f037
Fig 19-2 1H-NMR and 13C-NMR spectra of compound 19…………………..f038
Fig 20-1 MS and IR spectra of compound 20………………………………...f039
Fig 20-2 1H-NMR and 13C-NMR spectra of compound 20………………..…f040
Fig 21-1 MS and IR spectra of compound 21…………………………………f041
Fig 21-2 1H-NMR and 13C-NMR spectra of compound 21…………………..f042
Fig 22-1 MS and IR spectra of compound 22…………………………….…..f043
Fig 22-2 1H-NMR and 13C-NMR spectra of compound 22…………………..f044
Fig 23-1 MS and IR spectra of compound 23…………………………….…..f045
Fig 23-2 1H-NMR and 13C-NMR spectra of compound 23…………………..f046
Fig 24-1 MS and IR spectra of compound 24…………………………….….. f047
Fig 24-2 1H-NMR and 13C-NMR spectra of compound 24…………………..f048
Fig 25-1 MS and IR spectra of compound 25………………………………...f049
Fig 25-2 1H-NMR and 13C-NMR spectra of compound 25…………………..f050
Fig 26-1 MS and IR spectra of compound 26………………………….……..f051
Fig 26-2 1H-NMR and 13C-NMR spectra of compound 26………………..…f052
Fig 27-1 MS and IR spectra of compound 27………………………………...f053
Fig 27-2 1H-NMR and 13C-NMR spectra of compound 27………………..…f054
Fig 28-1 MS and IR spectra of compound 28………………………………...f055
Fig 28-2 1H-NMR and 13C-NMR spectra of compound 28…………………..f056
Fig 29-1 MS and IR spectra of compound 29………………………………...f057
Fig 29-2 1H-NMR and 13C-NMR spectra of compound 29………………..…f058
Fig 30-1 MS and IR spectra of compound 30………………………………...f059
Fig 30-2 1H-NMR and 13C-NMR spectra of compound 30…………………..f060
Fig 31-1 MS and IR spectra of compound 31…………………………………f061
Fig 31-2 1H-NMR and 13C-NMR spectra of compound 31…………………..f062
Fig 32-1 MS and IR spectra of compound 32…………………………….…..f063
Fig 32-2 1H-NMR and 13C-NMR spectra of compound 32…………………..f064
Fig 33-1 MS and IR spectra of compound 33…………………………….…..f065
Fig 33-2 1H-NMR and 13C-NMR spectra of compound 33…………………..f066
Fig 34-1 MS and IR spectra of compound 34……………………………… ..f067
Fig 34-2 1H-NMR and 13C-NMR spectra of compound 34……………….….f068
Fig 35-1 MS and IR spectra of compound 35………………………………...f069
Fig 35-2 1H-NMR and 13C-NMR spectra of compound 35…………………..f070
Fig 36-1 MS and IR spectra of compound 36……………………………...…f071
Fig 36-2 1H-NMR and 13C-NMR spectra of compound 36…………………..f072
Fig 37-1 MS and IR spectra of compound 37………………………………...f073
Fig 37-2 1H-NMR and 13C-NMR spectra of compound 37…………………..f074
Fig 38-1 MS and IR spectra of compound 38…………………………….…..f075
Fig 38-2 1H-NMR and 13C-NMR spectra of compound 38…………………..f076
附錄二（結構部份）
Compound 1~12…………………………………………………………………..F077
Compound 13~25…………………………………………………………………F079
Compound 26~38…………………………………………………………………F081
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參考文獻
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