Scaffold Hopping and Optimization of Maleimide Based Porcupine Inhibitors
Porcupine is an O-acyltransferase that regulates Wnt secretion. Inhibiting porcupine may block the Wnt pathway which is often dysregulated in various cancers. Consequently porcupine inhibitors are thought to be promising oncology therapeutics. A high throughput screen against porcupine revealed several potent hits that were confirmed to be Wnt pathway inhibitors in secondary assays. We developed a pharmacophore model and used the putative bioactive conformation of a xanthine inhibitor for scaffold hopping. The resulting maleimide scaffold was optimized to subnanomolar potency while retaining good physical druglike properties. A preclinical development candidate was selected for which extensive in vitro and in vivo profiling is reported.
Ho, Soo Yei,Alam, Jenefer,Jeyaraj, Duraiswamy Athisayamani,Wang, Weiling,Lin, Grace Ruiting,Ang, Shi Hua,Tan, Eldwin Sum Wai,Lee, May Ann,Ke, Zhiyuan,Madan, Babita,Virshup, David M.,Ding, Li Jun,Manoharan, Vithya,Chew, Yun Shan,Low, Choon Bing,Pendharkar, Vishal,Sangthongpitag, Kanda,Hill, Jeffrey,Keller, Thomas H.,Poulsen, Anders
p. 6678 - 6692
(2017/08/18)
2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF
An efficient chemoselective nitrogen functionalization of phthalimides by using KF-Alumina in 2-methyltetrahydrofuran, a solvent obtained from renewal sources, is described.
Pace, Vittorio,Hoyos, Pilar,Fernandez, Maria,Sinisterra, Jose V.,Alcantara, Andres R.
supporting information; experimental part
p. 1380 - 1382
(2010/09/05)
3-AZABICYCLO [3.1.0] HEXANE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
The present invention relates to 3-azabicyclo[3.1.0]hexane derivatives, which are useful as vanilloid receptor (VR) ligands, methods of treating diseases, conditions and/or disorders modulated by vanilloid receptors with them, and processes for preparing them.
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Page/Page column 48
(2009/08/16)
NITRATION OF AROMATIC COMPOUNDS CATALYZED BY ZrO2/SO42-
Catalytic activity was demonstrated for zirconium dioxide, which is a solid acid, modified by sulfate ions in the nitration of inactive aromatic compounds.
Nagi, Sh. M.,Zubkov, E. A.,Shubin, V. G.
p. 1500 - 1502
(2007/10/02)
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