title: Synthesis of prolyl endopeptidase inhibitors and evaluation of their structure-activity relationships: in vitro inhibition of prolyl endopeptidase from canine brain.
abstract: 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.
authors.affiliation: Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: H
authors.initials: H
authors.lastname: Nishioka
authors.forename: S
authors.initials: S
authors.lastname: Niwa
authors.forename: T
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Miura
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: 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
chemical_list: D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; C074327:N-(N-(phenyl)butyryl-L-prolyl)pyrrolidine; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases