期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 20, 期 2, 页码 576-580出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.11.081
关键词
MMP; Osteoarthritis; DMOAD
Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)' active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model. (C) 2009 Elsevier Ltd. All rights reserved.
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