Thomson, Christopher, Le Grand, Darren, Dowling, Mark, Brocklehurst, Cara, Chinn, Colin, Elphick, Lucy, Faller, Michael, Freeman, Mark, Furminger, Vikki, Gasser, Cornelia, Hamadi, Ahmed, Hardaker, Elizabeth, Head, Victoria, Hill, Johan, Janus, Diana, Pearce, David, Poulaud, Anne-Sophie, Stanley, Emily and Sviridenko, Lilya (2018) Development of Autotaxin Inhibitors Part 1: A Series of Zinc Binding Triazoles. Bioorganic and medicinal chemistry letters, 28 (13). pp. 2279-2284.

Abstract

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 benzoxazolinone 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

Item Type:	Article
Date Deposited:	18 Aug 2018 00:45
Last Modified:	18 Aug 2018 00:45
URI:	https://oak.novartis.com/id/eprint/34936