1003872-51-2Relevant articles and documents
Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells
Jones, Stuart,Ahmet, Jonathan,Ayton, Kelly,Ball, Matthew,Cockerill, Mark,Fairweather, Emma,Hamilton, Nicola,Harper, Paul,Hitchin, James,Jordan, Allan,Levy, Colin,Lopez, Ruth,McKenzie, Eddie,Packer, Martin,Plant, Darren,Simpson, Iain,Simpson, Peter,Sinclair, Ian,Somervaille, Tim C.P.,Small, Helen,Spencer, Gary J.,Thomson, Graeme,Tonge, Michael,Waddell, Ian,Walsh, Jarrod,Waszkowycz, Bohdan,Wigglesworth, Mark,Wiseman, Daniel H.,Ogilvie, Donald
supporting information, p. 11120 - 11137 (2016/12/30)
A collaborative high throughput screen of 1.35 million compounds against mutant (R132H) isocitrate dehydrogenase IDH1 led to the identification of a novel series of inhibitors. Elucidation of the bound ligand crystal structure showed that the inhibitors exhibited a novel binding mode in a previously identified allosteric site of IDH1 (R132H). This information guided the optimization of the series yielding submicromolar enzyme inhibitors with promising cellular activity. Encouragingly, one compound from this series was found to induce myeloid differentiation in primary human IDH1 R132H AML cells in vitro.
Discovery of a potent, selective, and orally bioavailable acidic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor: Discovery of 2-[(3 s)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]- 3-piperidyl]acetic acid (AZD4017)
Scott, James S.,Bowker, Suzanne S.,Deschoolmeester, Joanne,Gerhardt, Stefan,Hargreaves, David,Kilgour, Elaine,Lloyd, Adele,Mayers, Rachel M.,McCoull, William,Newcombe, Nicholas J.,Ogg, Derek,Packer, Martin J.,Rees, Amanda,Revill, John,Schofield, Paul,Selmi, Nidhal,Swales, John G.,Whittamore, Paul R. O.
supporting information; experimental part, p. 5951 - 5964 (2012/08/07)
Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11β-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.
CHEMICAL COMPOUNDS
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Page/Page column 34, (2008/12/04)
Compounds of formula (I): wherein variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are described.
CHEMICAL COMPOUNDS 428
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Page/Page column 55-56, (2010/11/30)
Compounds of formula (I): wherein variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are described.
