Ontology highlight
ABSTRACT:
SUBMITTER: Rohde JM
PROVIDER: S-EPMC8968748 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Rohde Jason M JM Karavadhi Surendra S Pragani Rajan R Liu Li L Fang Yuhong Y Zhang Weihe W McIver Andrew A Zheng Hongchao H Liu Qingyang Q Davis Mindy I MI Urban Daniel J DJ Lee Tobie D TD Cheff Dorian M DM Hollingshead Melinda M Henderson Mark J MJ Martinez Natalia J NJ Brimacombe Kyle R KR Yasgar Adam A Zhao Wei W Klumpp-Thomas Carleen C Michael Sam S Covey Joseph J Moore William J WJ Stott Gordon M GM Li Zhuyin Z Simeonov Anton A Jadhav Ajit A Frye Stephen S Hall Matthew D MD Shen Min M Wang Xiaodong X Patnaik Samarjit S Boxer Matthew B MB
Journal of medicinal chemistry 20210406 8
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-2<i>H</i>-1λ<sup>2</sup>-quinoline-2,5(6<i>H</i>)-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 <b>(+)-119</b ...[more]