alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1

D P Becker; G DeCrescenzo; J Freskos; D P Getman; S L Hockerman; M Li; P Mehta; G E Munie; C Swearingen

doi:10.1016/s0960-894x(01)00557-1

alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1

Bioorg Med Chem Lett. 2001 Oct 22;11(20):2723-5. doi: 10.1016/s0960-894x(01)00557-1.

Authors

D P Becker¹, G DeCrescenzo, J Freskos, D P Getman, S L Hockerman, M Li, P Mehta, G E Munie, C Swearingen

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: 11591510
DOI: 10.1016/s0960-894x(01)00557-1

Abstract

A series of alpha-alkyl-alpha-amino-beta-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.

MeSH terms

Alkanes / chemistry
Alkanes / pharmacology*
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*
Structure-Activity Relationship

Substances

Alkanes
Enzyme Inhibitors
Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Collagenases
Matrix Metalloproteinase 13
Matrix Metalloproteinase 2
Matrix Metalloproteinase 1