Prolyl endopeptidase inhibitors.
Selective prolyl endopeptidase inhibitors were elaborated by modification of the structure of SUAM-1221, by using a CoMFA study and protein crystallography. The most active representatives of omega-(N-hetaryl)alkanoylprolylpyrrolidines, containing 2- or 3-methylene chain links have high activity (IC50 10(-9)-10(-11)) and exhibit significant in vivo activities.
CHINOIN Pharmaceutical and Chemical Works Ltd., Budapest, Hungary. istvan.hermecz@sanofi-synthelabo.com
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D000818:Animals; D003461:Crystallography; D010450:Endopeptidases / Q000378:metabolism*; D066298:In Vitro Techniques; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; C074327:N-(N-(phenyl)butyryl-L-prolyl)pyrrolidine; D010450:Endopeptidases