- 作者: 陳基旺 ; 林華美 ; 鄭逢吉 ; 羅吉鈞 ; 賴南褘 ; 高佳麟
- 作者服務機構: 台灣大學藥學系
- 中文摘要: In the course of our investigations on the development of cardiovascular agents, 3-butyl-2-[2'-(2H-tetrazol-5-yl) biphenyl-4-yl] methyl-2H-l,2,4-benzothiadiazine 1,1-dioxide (2) was considered as a potential angiotensin II antagonist on the basis of bioisosteric replacement of the quinazoline ring of compound 1 with a 1,2,4-benzothiadiazine 1,1-dioxide ring system. Alkylation of 6 with 4 afforded 7 and 8 in 24% and 28% yields, respectively. An attempt to remove the trityl group of compounds 7 and 8 under acidic condition gave the ring opened products 9 and 11 in 28% and 36% yields, respectively. However, compounds 2 and 10 were obtained in 46% and 85% yields when compounds 7 and 8 were refluxed in methanol. Preliminary assays of compounds 9 and 11 against angiotensin II receptors revealed weak activity with IC/sub 50/ values of 3.6.mu.M and 5.4 .mu.M, respectively. Compound 10 (IC/sub 50/ = 87nM) exhibited stronger binding affinity than compound 2 (IC/ sub 50/ = 750nM).
- 英文摘要: --
- 中文關鍵字: Angiotensin; Benzothiadiazine; Antagonist; Biphenyltetrazole
- 英文關鍵字: 血管緊縮素;苯並吩重氮;拮抗劑;二苯基四唑