摘要
以天然血管紧张素转化酶抑制剂(ACEI)I_5B_2,WF-10129为先导化合物,结合现有ACEI的结构特征,设计和合成了含缬-酪-酪(Ⅰ_(1～4))和缬(丙)-酪(Ⅱ_(1～6))肽类化合物。初步药理试验表明,Ⅱ类化合物体外均有不同程度抑制ACE的活性,其中以Ⅱ_5活性最强(IC_(50)=7.9×10^(-10)mol/L),体内抑制血管紧张素Ⅰ(AI)的升压活性也以Ⅱ_5和Ⅱ_4最强,与卡托普利相仿。
I5B2 and WF-10129, reported as potent angiotensin-converting enzyme inhibitors (ACEI), were used as lead compounds for design of novel ACEI. Some of Val-Tyr-Tyr and Val-Tyrpeptides were synthesized and tested for ability to inhibit ACE in vitro and in Vivo. The most potent com-pound was found to be N-(1-benzoyl-1-carboxylmethyl)-L-Alayl-L-Tyrosine (II_5, IC_(50)=7.9×10^(-10)mol/L) which was prepared by the addition of Ala-Tyr to benzoylacrylic acid in the presence of triethy-lamine. The structure-activity relationships were also discussed.
出处
《药学学报》
CAS
CSCD
北大核心
1992年第12期895-902,共8页
Acta Pharmaceutica Sinica
关键词
缬-酪-酪肽类
构效关系
合成
Angiotensin--converting enzyme inhibitors
Val--Tyr--Tyr peptides
Val (Ala)--Tyr peptides
Structure--activity relationships
