- Fatty acid amide hydrolase inhibitors. 3: Tetra-substituted azetidine ureas with in vivo activity
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We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.
- Roughley, Stephen D.,Browne, Helen,MacIas, Alba T.,Benwell, Karen,Brooks, Teresa,D'Alessandro, Jalanie,Daniels, Zoe,Dugdale, Sarah,Francis, Geraint,Gibbons, Ben,Hart, Terance,Haymes, Timothy,Kennett, Guy,Lightowler, Sean,Matassova, Natalia,Mansell, Howard,Merrett, Angela,Misra, Anil,Padfield, Anthony,Parsons, Rachel,Pratt, Robert,Robertson, Alan,Simmonite, Heather,Tan, Kiri,Walls, Steven B.,Wong, Melanie
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p. 901 - 906
(2012/03/11)
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- Addition of Grignard reagents to aryl acid chlorides: An efficient synthesis of aryl ketones
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(Chemical Equation Presented) Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.
- Wang, Xiao-Jun,Zhang, Li,Sun, Xiufeng,Xu, Yibo,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
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p. 5593 - 5595
(2007/10/03)
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- Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation
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Synthesis of 2-aminoimidazo[1,2-a]pyridines 1 and their evaluation as CDK2 inhibitors is described. We have identified a novel structural class of protein serine/threonine kinase inhibitors comprised of an aminoimidazo[1,2-a]pyridine nucleus. Compounds from this family are shown to potently inhibit cyclin-dependent kinases by competing with ATP for binding to a catalytic subunit of the protein. Structure-based design approach was used to direct this chemical scaffold toward generating potent and selective CDK2 inhibitors. The discovery of this new class of ATP-site directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis of new medicinal chemistry tool in search for an effective treatment of cancer and other diseases that involve protein kinase signaling pathways.
- Jaramillo, Carlos,De Diego, J. Eugenio,Hamdouchi, Chafiq,Collins, Elizabeth,Keyser, Heather,Sánchez-Martínez, Concha,Del Prado, Miriam,Norman, Bryan,Brooks, Harold B.,Watkins, Scott A.,Spencer, Charles D.,Dempsey, Jack Alan,Anderson, Bryan D.,Campbell, Robert M.,Leggett, Tellie,Patel, Bharvin,Schultz, Richard M.,Espinosa, Juan,Vieth, Michal,Zhang, Faming,Timm, David E.
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p. 6095 - 6099
(2007/10/03)
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