Poststatin, a New Inhibitor of Prolyl Endopeptidase

VII. N-Cycloalkylamide Analogues

抄録

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 P'₁ was effective and P₃-acyl groups must be widely modifiable for prolyl endopeptidase inhibition. Acyl-L-phenylalanyl-(S)-2-oxo-2-(2-pyrrolidinyl)acetyl-cycloalkylamide 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.