Tsuda M, Muraoka Y, Nagai M, Aoyagi T, Takeuchi T
Institute of Microbial Chemistry, Tokyo, Japan.
J Antibiot (Tokyo). 1996 Sep;49(9):909-20. doi: 10.7164/antibiotics.49.909.
Poststatin analogues containing (S)-2-oxo-2-(2-pyrrolidinyl)acetyl moiety in P1 were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Introduction of non-peptidyl cycloalkylamine component in P1, was effective and P3-acyl groups must be widely modifiable for prolyl endopeptidase inhibition. Acyl-L-phenylalanyl-(S)-2-oxo-2-(2-pyrrolidinyl)acetyl-cycloalkylamid e type compounds showed IC50 value of nano to subnano g/ml as prolyl endopeptidase inhibitor and were shown no significant inhibitory activities against cathepsin B, a cysteine protease.
合成了在P1中含有(S)-2-氧代-2-(2-吡咯烷基)乙酰基部分的他汀类似物，并在体外检测了它们对脯氨酰内肽酶和组织蛋白酶B的抑制活性。在P1中引入非肽基环烷基胺成分是有效的，并且P3-酰基对于脯氨酰内肽酶抑制必须具有广泛的可修饰性。酰基-L-苯丙氨酰-(S)-2-氧代-2-(2-吡咯烷基)乙酰基-环烷基酰胺类化合物作为脯氨酰内肽酶抑制剂显示出纳克/毫升至亚纳克/毫升的IC50值，并且对组织蛋白酶B（一种半胱氨酸蛋白酶）没有显著的抑制活性。
