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Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1″ binding site.

Abstract：

:On the basis of X-ray co-crystal structures of matrix metalloproteinase-13 (MMP-13) in complex with its inhibitors, our structure-based drug design (SBDD) strategy was directed to achieving high affinity through optimal protein-ligand interaction with the unique S1″ hydrophobic specificity pocket. This report details the optimization of lead compound 44 to highly potent and selective MMP-13 inhibitors based on fused pyrimidine scaffolds represented by the thienopyrimidin-4-one 26c. Furthermore, we have examined the release of collagen fragments from bovine nasal cartilage in response to a combination of IL-1 and oncostatin M.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Nara H,Sato K,Naito T,Mototani H,Oki H,Yamamoto Y,Kuno H,Santou T,Kanzaki N,Terauchi J,Uchikawa O,Kori M

doi

10.1016/j.bmc.2014.07.025

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

5487-505

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00541-0

journal_volume

22

pub_type

杂志文章

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