- Development of autotaxin inhibitors: A series of zinc binding triazoles
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A series of inhibitors of Autotaxin (ATX) has been developed using the binding mode of known inhibitor, PF-8380, as a template. Replacement of the benzoxazolone with a triazole zinc-binding motif reduced crystallinity and improved solubility relative to PF-8380. Modification of the linker region removed hERG activity and led to compound 12 – a selective, high affinity, orally-bioavailable inhibitor of ATX. Compound 12 concentration-dependently inhibits autotaxin and formation of LPA in vivo, as shown in pharmacokinetic-pharmacodynamic experiments.
- Thomson, Christopher G.,Le Grand, Darren,Dowling, Mark,Brocklehurst, Cara E.,Chinn, Colin,Elphick, Lucy,Faller, Michael,Freeman, Mark,Furminger, Vikki,Gasser, Cornelia,Hamadi, Ahmed,Hardaker, Elizabeth,Head, Victoria,Hill, Johan C.,Janus, Diana I.,Pearce, David,Poulaud, Anne-Sophie,Stanley, Emily,Sviridenko, Lilya
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supporting information
p. 2279 - 2284
(2018/05/24)
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- AUTOTAXIN INHIBITORS COMPRISING A HETEROAROMATIC RING-BENZYL-AMIDE-CYCLE CORE
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The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.
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Page/Page column 296
(2015/02/02)
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- Autotaxin inhibitors
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The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.
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Page/Page column
(2014/06/25)
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