摘要
粉防己碱有较好的钙拮抗作用,临床上已试用于治疗高血压,为简化结构,将粉防己碱还原裂解,以裂解产物为先导物,设计合成了一系列取代的四氢异喹啉衍生物,其中86040经药效学研究表明,静注或口服给药,对正常和高血压大鼠都有降压作用,本文还探讨了86040构象对活性的可能影响。
Tetrandrine possesses calcium antagonistic activity and hypotensive effects. For modification of the structure, it was cleaved into two components (Ⅱ_1 and Ⅱ_2) by reduction. With cleavage products as lead compounds, a series of substitued tetrahydroisoquinoline derivatives were designed and synthesized as novel potential cardiovascular drugs. One of these compounds, 1-(α-naphthylmethyl)-2-methyl-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (86040) showed hypotensive effects on either normal rats or SHR by iv and po administration. X-ray crystallogram of 86040 hydrobromide was determined and compared with those of tetrandrine, coclaurine (the structure analogue of Ⅱ_2). A torsion angle between isoquinoline ring and aromatic ring for 86040 (25.8°) was smaller than that of tetrandrine (26°), both possessing calcium antagonistic and hypotensive effects; but it was 90° for effectiveless coclaurine.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
1992年第6期321-324,共4页
Journal of China Pharmaceutical University
关键词
粉防己碱
四氢异喹啉
降压药
1- (α-naphthylmethyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride
Tetrandrine
Tetrahydroisoquinoline
Hypotensive activity
X-ray crystallogram
