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

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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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