α-Alkyl-α-amino-β-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1

A series of α-alkyl-α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. α-Alkyl...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2001-10, Vol.11 (20), p.2723-2725
Main Authors: Becker, Daniel P, DeCrescenzo, Gary, Freskos, John, Getman, Daniel P, Hockerman, Susan L, Li, Madeleine, Mehta, Pramod, Munie, Grace E, Swearingen, Craig
Format: Article
Language:English
Subjects:
Alkanes - chemistry
Alkanes - pharmacology
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Collagenases - metabolism
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Hydroxamic Acids - chemistry
Hydroxamic Acids - pharmacology
Inhibitory Concentration 50
Matrix Metalloproteinase 1 - metabolism
Matrix Metalloproteinase 13
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase Inhibitors
Medical sciences
Pharmacology. Drug treatments
Structure-Activity Relationship
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:A series of α-alkyl-α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. α-Alkyl-α-amino-β-sulphone hydroxamates were prepared, which are potent MMP-2 and MMP-13 inhibitors with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(01)00557-1