52353-66-9Relevant articles and documents
Discovery and Optimization of 2 H-1λ2-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer
Rohde, Jason M.,Karavadhi, Surendra,Pragani, Rajan,Liu, Li,Fang, Yuhong,Zhang, Weihe,McIver, Andrew,Zheng, Hongchao,Liu, Qingyang,Davis, Mindy I.,Urban, Daniel J.,Lee, Tobie D.,Cheff, Dorian M.,Hollingshead, Melinda,Henderson, Mark J.,Martinez, Natalia J.,Brimacombe, Kyle R.,Yasgar, Adam,Zhao, Wei,Klumpp-Thomas, Carleen,Michael, Sam,Covey, Joseph,Moore, William J.,Stott, Gordon M.,Li, Zhuyin,Simeonov, Anton,Jadhav, Ajit,Frye, Stephen,Hall, Matthew D.,Shen, Min,Wang, Xiaodong,Patnaik, Samarjit,Boxer, Matthew B.
, p. 4913 - 4946 (2021/05/07)
Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are oncogenic for a number of malignancies, primarily low-grade gliomas and acute myeloid leukemia. We report a medicinal chemistry campaign around a 7,7-dimethyl-7,8-dihydro-2H-1λ2-quinoline-2,5(6H)-dione screening hit against the R132H and R132C mutant forms of isocitrate dehydrogenase (IDH1). Systematic SAR efforts produced a series of potent pyrid-2-one mIDH1 inhibitors, including the atropisomer (+)-119 (NCATS-SM5637, NSC 791985). In an engineered mIDH1-U87-xenograft mouse model, after a single oral dose of 30 mg/kg, 16 h post dose, between 16 and 48 h, (+)-119 showed higher tumoral concentrations that corresponded to lower 2-HG concentrations, when compared with the approved drug AG-120 (ivosidenib).
5-Substituted imidazole-4-acetic acid analogues: Synthesis, modeling, and pharmacological characterization of a series of novel γ-aminobutyric acidC receptor agonists
Madsen, Christian,Jensen, Anders A.,Liljefors, Tommy,Kristiansen, Uffe,Nielsen, Birgitte,Hansen, Camilla P.,Larsen, Mogens,Ebert, Bjarke,Bang-Andersen, Benny,Krogsgaard-Larsen, Povl,Fr?lund, Bente
, p. 4147 - 4161 (2008/02/13)
A series of ring-substituted analogues of imidazole-4-acetic acid (IAA, 4), a partial agonist at both GABAA and GABAC receptors (GABA = γ-aminobutyric acid), have been synthesized. The synthesized compounds 8a-1 have been evaluated a
