On February 9, 2017, Levell, Julian R.; Caferro, Thomas; Chenail, Gregg; Dix, Ina; Dooley, Julia; Firestone, Brant; Fortin, Pascal D.; Giraldes, John; Gould, Ty; Growney, Joseph D.; Jones, Michael D.; Kulathila, Raviraj; Lin, Fallon; Liu, Gang; Mueller, Arne; van der Plas, Simon; Slocum, Kelly; Smith, Troy; Terranova, Remi; Toure, B. Barry; Tyagi, Viraj; Wagner, Trixie; Xie, Xiaoling; Xu, Ming; Yang, Fan S.; Zhou, Liping X.; Pagliarini, Raymond; Cho, Young Shin published an article.Computed Properties of 168297-86-7 The title of the article was Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1. And the article contained the following:
High throughput screening and subsequent hit validation identified 4-isopropyl-3-(2-((1-phenylethyl)amino)pyrimidin-4-yl)oxazolidin-2-one as a potent inhibitor of IDH1R132H. Synthesis of the four sep. stereomers identified the (S,S)-diastereomer (IDH125, 1f) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs. IDH1wt. Initial SAR exploration identified the key tolerances and potential for optimization. X-ray crystallog. identified a functionally relevant allosteric binding site amenable to inhibitors which can penetrate the blood-brain barrier, and aided rational optimization. Potency improvement and modulation of the physico-chem. properties identified (S,S)-oxazolidinone IDH889 (5x) with good exposure and 2-HG inhibitory activity in a mutant IDH1 xenograft mouse model. The experimental process involved the reaction of (S)-4-Isopropyl-5,5-dimethyloxazolidin-2-one(cas: 168297-86-7).Computed Properties of 168297-86-7
The Article related to pyrimidinyloxazolidinone preparation allosteric inhibitor isocitrate dehydrogenase idh1, 2-hg, 3-pyrimidin-4-yloxazolidin-2-one, mutant idh1 inhibitor, allosteric inhibition, chirality-defined potency, preclinical in vivo activity and other aspects.Computed Properties of 168297-86-7
Referemce:
Oxazolidine – Wikipedia,
Oxazolidine | C3H7NO – PubChem