On December 1, 2019, Cao, Hengyi; Zhu, Guangya; Sun, Lin; Chen, Ge; Ma, Xinxin; Luo, Xiao; Zhu, Jidong published an article.Formula: C8H15NO2 The title of the article was Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration. And the article contained the following:
Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5, (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(7-(trifluoromethyl)4,5-dihydroimidazo[1,5-a]quinolin-3-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one [2379528-08-0], exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclin. candidate to treat IDH1-mutant brain tumors. The experimental process involved the reaction of (S)-4-Isopropyl-5,5-dimethyloxazolidin-2-one(cas: 168297-86-7).Formula: C8H15NO2
The Article related to glioblastoma antitumor pharmacokinetics isocitrate dehydrogenase 1 blood brain barrier, acute myeloid leukemia, blood-brain barrier, cancer therapy, glioblastoma, isocitrate dehydrogenase 1, small molecule inhibitors and other aspects.Formula: C8H15NO2
Referemce:
Oxazolidine – Wikipedia,
Oxazolidine | C3H7NO – PubChem