Synthesis of prolyl endopeptidase inhibitors and evaluation of their structure-activity relationships: in vitro inhibition of prolyl endopeptidase from canine brain.
By chemical modification of a known prolyl endopeptidase (PEP) inhibitor (N-[N-(4-phenylbutanoyl)-L-prolyl]pyrrolidine; SUAM-1221), several arylalkanoyl derivatives (V-1--27) were synthesized and tested for in vitro inhibitory activity towards PEP from canine brain. Among them, 4-(2-thienyl)butanoyl derivatives (V-24--27) showed more potent PEP-inhibitory activity than SUAM-1221. The structure-activity relationships of these compounds are discussed.
Arai
H
H
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Nishioka
H
H
Niwa
S
S
Yamanaka
T
T
Tanaka
Y
Y
Yoshinaga
K
K
Kobayashi
N
N
Miura
N
N
Ikeda
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004285:Dogs; D008969:Molecular Sequence Data; D000085822:Prolyl Oligopeptidases; D011758:Pyrroles / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; C074327:N-(N-(phenyl)butyryl-L-prolyl)pyrrolidine; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases