哒嗪酮类α1-肾上腺素受体拮抗剂的合成和生物活性研究有机化学.pdfVIP

2006 年第 26 卷 有 机 化 学 Vol. 26, 2006 第 11 期, 1576～1583 Chinese Journal of Organic Chemistry No. 11, 1576～1583 ·研究论文· 哒嗪酮类 α -肾上腺素受体拮抗剂的合成和生物活性研究 1 习保民 a 江振洲 b 王 涛 b 倪沛州*,c (a 中国药科大学物理化学教研室 南京 210038) (b 中国药科大学新药筛选中心 南京 210038) (c 中国药科大学有机化学教研室 南京 210038) 摘要 将苯(氧) 乙胺和苯氧烷胺类 α1- 肾上腺素受体拮抗剂中的苯(氧) 乙胺、苯氧烷胺片段引入哒嗪酮类化合物中, 设 计、合成了 30 个新的含哒嗪酮环的 α1- 肾上腺素受体拮抗剂. 所有新化合物的结构均经 1H NMR, IR, HRMS 确证. 生物 活性测试表明 28 个目标物对 α1- 肾上腺素受体有较好的拮抗作用(pA2 ＞6.00), 化合物 6o, 6p, 6q, 6v, 6x, 6y, 10c, 10d 的 pA2 值＞7.00. 关键词 哒嗪酮; 合成; 生物活性; α1- 肾上腺素受体拮抗剂 Studies on Synthesis and Biological Activity of Pyridazinone Derivatives as α1-Adrenoceptor Antagonist XI, Bao-Mina JIANG, Zhen-Zhoub WANG, Taob NI, Pei-Zhou*,c a ( Department of Physical Chemistry, China Pharmaceutical University, Nanjing 210038) (b National Drug Screening Center , China Pharmaceutical University, Nanjing 210038) (c Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210038) Abstract Phenylethylamine and phenoxylalkylamine fragments were introduced into pyridazinone deriva- tives (as α1-adrenoceptor antagonist) for the first time. 30 new compounds of pyridazinone were designed 1 and synthesized. The structures of the new compounds were identified by H NMR, I