2923-99-1Relevant academic research and scientific papers
COMPOUNDS AND COMPOSITIONS AS MODULATORS OF TLR SIGNALING
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Paragraph 0406, (2020/10/20)
The present disclosure relates to compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins.
Atropisomer Control in Macrocyclic Factor VIIa Inhibitors
Glunz, Peter W.,Mueller, Luciano,Cheney, Daniel L.,Ladziata, Vladimir,Zou, Yan,Wurtz, Nicholas R.,Wei, Anzhi,Wong, Pancras C.,Wexler, Ruth R.,Priestley, E. Scott
supporting information, p. 4007 - 4018 (2016/05/19)
Incorporation of a methyl group onto a macrocyclic FVIIa inhibitor improves potency 10-fold but is accompanied by atropisomerism due to restricted bond rotation in the macrocyclic structure, as demonstrated by NMR studies. We designed a conformational constraint favoring the desired atropisomer in which this methyl group interacts with the S2 pocket of FVIIa. A macrocyclic inhibitor incorporating this constraint was prepared and demonstrated by NMR to reside predominantly in the desired conformation. This modification improved potency 180-fold relative to the unsubstituted, racemic macrocycle and improved selectivity. An X-ray crystal structure of a closely related analogue in the FVIIa active site was obtained and matches the NMR and modeled conformations, confirming that this conformational constraint does indeed direct the methyl group into the S2 pocket as designed. The resulting rationally designed, conformationally stable template enables further optimization of these macrocyclic inhibitors.
MACROCYCLIC FACTOR VIIA INHIBITORS
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Paragraph 00176, (2015/01/09)
The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.
MACROCYCLIC FACTOR VIIA INHIBITORS
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Paragraph 00277; 00278, (2014/01/08)
The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.
