title: Synthesis of triazole-Tethered pyrrolidine libraries: novel ECE inhibitors.
abstract: The solid-phase synthesis of substituted 1,2,4-triazoles tethered to a 4-mercaptopyrrolidine core 1 is described. This novel class of non-peptidic, Zn(2+) metallo-protease inhibitors was found to have inhibitory activity for the endothelin converting enzyme (ECE-1). The SAR of the substitution pattern in 1 is discussed.
authors.affiliation: Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., CH-4070, Basel, Switzerland. eric_a.kitas@roche.com
authors.forename: Eric A
authors.initials: EA
authors.lastname: Kitas
authors.forename: Bernd-Michael
authors.initials: BM
authors.lastname: Löffler
authors.forename: Stefan
authors.initials: S
authors.lastname: Daetwyler
authors.forename: Henrietta
authors.initials: H
authors.lastname: Dehmlow
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Aebi
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D020128:Inhibitory Concentration 50; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D011759:Pyrrolidines; D014230:Triazoles; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes