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 patter...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2002-07, Vol.12 (13), p.1727-1730
Main Authors: Kitas, Eric A, Löffler, Bernd-Michael, Daetwyler, Stefan, Dehmlow, Henrietta, Aebi, Johannes D
Format: Article
Language:English
Subjects:
Aspartic Acid Endopeptidases - antagonists & inhibitors
Biological and medical sciences
Cardiovascular system
Endothelin-Converting Enzymes
Humans
Inhibitory Concentration 50
Medical sciences
Metalloendopeptidases - antagonists & inhibitors
Pharmacology. Drug treatments
Protease Inhibitors - chemical synthesis
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Pyrrolidines - chemical synthesis
Pyrrolidines - chemistry
Pyrrolidines - pharmacology
Structure-Activity Relationship
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
Vasodilator agents. Cerebral vasodilators
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Compound libraries with general structure 1 were synthesized on solid support. They were found to be a new class of ECE-1 inhibitors.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(02)00254-8