862118-89-6Relevant academic research and scientific papers
SELECTIVE MATRIX METALLOPROTEINASE-13 INHIBITORS
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Paragraph 00149; 00150, (2019/01/06)
We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative
Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors
Choi, Jun Yong,Fuerst, Rita,Knapinska, Anna M.,Taylor, Alexander B.,Smith, Lyndsay,Cao, Xiaohang,Hart, P. John,Fields, Gregg B.,Roush, William R.
supporting information, p. 5816 - 5825 (2017/07/22)
We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative
SAR studies of non-zinc-chelating MMP-13 inhibitors: Improving selectivity and metabolic stability
Gao, Donghong Amy,Xiong, Zhaoming,Heim-Riether, Alexander,Amodeo, Laura,August, E. Michael,Cao, Xianhua,Ciccarelli, Leonard,Collins, Brandon K.,Harrington, Kyle,Haverty, Kathleen,Hill-Drzewi, Melissa,Li, Xiang,Liang, Shuang,Margarit, Steluta Mariana,Moss, Neil,Nagaraja, Nelamangala,Proudfoot, John,Roman, Rene,Schlyer, Sabine,Keenan, Lana Smith,Taylor, Steven,Wellenzohn, Bernd,Wiedenmayer, Dieter,Li, Jun,Farrow, Neil A.
scheme or table, p. 5039 - 5043 (2010/10/18)
SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1′ pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound.
HCV NS-3 serine protease inhibitors
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, (2008/06/13)
HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, having the formula I wherein A is
HCV NS-3 serine protease inhibitors
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, (2008/06/13)
HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, of formula: wherein A is
Squaric acid-based peptidic inhibitors of matrix metalloprotease-1
Onaran, M. Burak,Comeau, Anthony B.,Seto, Christopher T.
, p. 10792 - 10802 (2007/10/03)
A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1′ and S2′ subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 μM. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 μM.
HCV NS-3 SERINE PROTEASE INHIBITORS
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Page/Page column 97, (2008/06/13)
Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.
