Title of article
N-((8-Hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2)
Author/Authors
Adam M. Gilbert، نويسنده , , Matthew G. Bursavich، نويسنده , , Sabrina Lombardi، نويسنده , , Katy E. Georgiadis، نويسنده , , Erica Reifenberg، نويسنده , , Carl R. Flannery، نويسنده , , Elisabeth A. Morris، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2008
Pages
4
From page
6454
To page
6457
Abstract
N-((8-Hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared. Selected compounds 10, 14, 25, and 53 show sub-μM ADAMTS-5 potency and good selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP-13, and MMP-12. Compound 53 shows a good balance of potent ADAMTS-5 inhibition, moderate CYP3A4 inhibition and good rat liver microsome stability. This series of compounds represents progress towards selective ADAMTS-5 inhibitors as disease modifying osteoarthritis agents.
Keywords
Aggrecanase-2 , ADAMTS-4 , Aggrecanase-1 , osteoarthritis , metalloproteases , ADAMTS-5
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2008
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
800257
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