alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

D P Becker; T E Barta; L Bedell; G DeCrescenzo; J Freskos; D P Getman; S L Hockerman; M Li; P Mehta; B Mischke; G E Munie; C Swearingen; C I Villamil

doi:10.1016/s0960-894x(01)00556-x

alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

Bioorg Med Chem Lett. 2001 Oct 22;11(20):2719-22. doi: 10.1016/s0960-894x(01)00556-x.

Authors

D P Becker¹, T E Barta, L Bedell, G DeCrescenzo, J Freskos, D P Getman, S L Hockerman, M Li, P Mehta, B Mischke, G E Munie, C Swearingen, C I Villamil

Affiliation

¹ Departments of Medicinal Chemistry and Inflammation-Oncology, Pharmacia Research & Development, 4901 Searle Parkway, Skokie, IL 60077, USA. daniel.p.becker@pharmacia.com

PMID: 11591509
DOI: 10.1016/s0960-894x(01)00556-x

Abstract

A series of alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the alpha-amino group (P(1) position), as well as different groups attached to the sulphone group extending into P(1)'. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000x for a number of analogues.

MeSH terms

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 Inhibitors*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Collagenases
Matrix Metalloproteinase 13
Matrix Metalloproteinase 1