473438-03-8Relevant articles and documents
Discovery of novel, highly potent, and selective matrix metalloproteinase (MMP)-13 inhibitors with a 1,2,4-triazol-3-yl moiety as a zinc binding group using a structure-based design approach
Nara, Hiroshi,Kaieda, Akira,Sato, Kenjiro,Naito, Takako,Mototani, Hideyuki,Oki, Hideyuki,Yamamoto, Yoshio,Kuno, Haruhiko,Santou, Takashi,Kanzaki, Naoyuki,Terauchi, Jun,Uchikawa, Osamu,Kori, Masakuni
, p. 608 - 626 (2017/02/05)
On the basis of a superposition study of X-ray crystal structures of complexes of quinazoline derivative 1 and triazole derivative 2 with matrix metalloproteinase (MMP)-13 catalytic domain, a novel series of fused pyrimidine compounds which possess a 1,2,4-triazol-3-yl group as a zinc binding group (ZBG) was designed. Among the herein described and evaluated compounds, 31f exhibited excellent potency for MMP-13 (IC50 = 0.036 nM) and selectivities (greater than 1,500-fold) over other MMPs (MMP-1, -2, -3, -7, -8, -9, -10, and -14) and tumor necrosis factor-α converting enzyme (TACE). Furthermore, the inhibitor was shown to protect bovine nasal cartilage explants against degradation induced by interleukin-1 and oncostatin M. In this article, we report the discovery of extremely potent, highly selective, and orally bioavailable fused pyrimidine derivatives that possess a 1,2,4-triazol-3-yl group as a novel ZBG for selective MMP-13 inhibition.
RETINOID-RELATED ORPHAN RECEPTOR GAMMA MODULATORS, COMPOSITION CONTAINING THEM AND USES THEREOF
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Page/Page column 14, (2012/08/08)
Provided are retinoid-related orphan receptor gamma(ROR γ) modulators of formula (I), processes for their preparation, pharmaceutical compositions containing them, and their uses in the treatment of diseases mediated by ROR γ.
HETEROCYCLIC AMIDE COMPOUND AND USE THEREOF
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Page/Page column 143, (2008/12/07)
The present invention provides a novel amide compound represented by the following formula, which has a matrix metalloproteinase inhibitory activity and is useful as a pharmaceutical agent. wherein each symbol is as defined in the specification.