Poststatin, a new inhibitor of prolyl endopeptidase. VII. N-cycloalkylamide analogues.
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.
Tsuda
M
M
Institute of Microbial Chemistry, Tokyo, Japan.
Muraoka
Y
Y
Nagai
M
M
Aoyagi
T
T
Takeuchi
T
T
D002401:Cathepsin B / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
C102426:N-(4-chlorobenzyl)-4-(2-(2-cyclohexylamino-1,2-dioxoethyl)pyrrolidin-1-yl)-4-oxobutanamide; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D013386:Succinates; C071400:poststatin; D011392:Proline; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D002401:Cathepsin B