Synthesis of triazole-Tethered pyrrolidine libraries: novel ECE inhibitors.
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.
Kitas
Eric A
EA
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., CH-4070, Basel, Switzerland. eric_a.kitas@roche.com
Löffler
Bernd-Michael
BM
Daetwyler
Stefan
S
Dehmlow
Henrietta
H
Aebi
Johannes D
JD
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
D011480:Protease Inhibitors; D011759:Pyrrolidines; D014230:Triazoles; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes