Synthesis of Prolyl Endopeptidase Inhibitors and Evaluation of Their Structure-Activity Relationships : In Vitro Inhibition of Prolyl Endopeptidase from Canine Brain

Heihachiro ARAI; Hiroyasu NISHIOKA; Seiichi NIWA; Takeshi YAMANAKA; Yoshiaki TANAKA; Koji YOSHINAGA; Naomi KOBAYASHI; Naoyoshi MIURA; Yugo IKEDA

doi:10.1248/cpb.41.1583

Heihachiro ARAI, Hiroyasu NISHIOKA, Seiichi NIWA, Takeshi YAMANAKA, Yoshiaki TANAKA, Koji YOSHINAGA, Naomi KOBAYASHI, Naoyoshi MIURA, Yugo IKEDA

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Keywords: prolyl endopeptidase, inhibitor, structure-activity relationship, 4-phenylbutanoyl derivative, 4-(2-thienyl)butanoyl derivative

JOURNAL FREE ACCESS

1993 Volume 41 Issue 9 Pages 1583-1588

DOI https://doi.org/10.1248/cpb.41.1583

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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.

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