Potent P1' biphenylmethyl substituted aggrecanase inhibitors

Wenqing Yao; Michael Chao; Zelda R Wasserman; Rui Qin Liu; Maryanne B Covington; Robert Newton; David Christ; Ruth R Wexler; Carl P Decicco

doi:10.1016/s0960-894x(01)00704-1

Potent P1' biphenylmethyl substituted aggrecanase inhibitors

Bioorg Med Chem Lett. 2002 Jan 7;12(1):101-4. doi: 10.1016/s0960-894x(01)00704-1.

Authors

Wenqing Yao¹, Michael Chao, Zelda R Wasserman, Rui Qin Liu, Maryanne B Covington, Robert Newton, David Christ, Ruth R Wexler, Carl P Decicco

Affiliation

¹ Department of Chemistry, Bristol-Myers Squibb Pharma Company, Experimental Station, Wilmington, DE 19880-0500, USA. wenping.yao@dupontpharma.com

PMID: 11738583
DOI: 10.1016/s0960-894x(01)00704-1

Abstract

A series of cis-1(S)2(R)-amino-2-indanol based compounds with a biphenylmethyl group at the P1' position was found to be potent aggrecanase inhibitors. Both compounds 2j and 2n possessed very high aggrecanase affinity (IC(50)=1.5nM), and showed excellent selectivity over MMP-1 and MMP-9, with moderate selectivity against MMP-2.

MeSH terms

Antirheumatic Agents / chemical synthesis
Antirheumatic Agents / chemistry
Antirheumatic Agents / metabolism
Biphenyl Compounds / chemistry*
Catalytic Domain
Drug Design
Drug Evaluation, Preclinical
Endopeptidases / chemistry*
Humans
Inhibitory Concentration 50
Metalloendopeptidases / metabolism
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / metabolism
Structure-Activity Relationship
Substrate Specificity

Substances

Antirheumatic Agents
Biphenyl Compounds
Protease Inhibitors
Endopeptidases
Metalloendopeptidases
aggrecanase