Zhao, Peng; Wang, Xiangzhu; Zhuang, Linghang; Huang, Song; Zhou, Yu; Yan, Yuna; Shen, Ru; Zhang, Fan; Li, Jie; Hu, Qiyue; Liu, Suxing; Zhang, Rumin; Dong, Ping; Wan, Hong; Bai, Chang; He, Feng; Tao, Weikang published the artcile< Discovery of novel spiro compound as RAF kinase inhibitor with in vitro potency against KRAS mutant cancer>, Synthetic Route of 112253-70-0, the main research area is RAF kinase inhibitor KRAS mutant cancer; Kinase inhibitor; Mutation; Paradoxical activation; RAF; RAS; Spiro compound.
The development of RAF inhibitors targeting cancers with wild type RAF kinase and/or RAS mutation has been challenging due to the paradoxical activation of the RAS-RAF-MEK-ERK cascade following RAF inhibitor treatment. Herein is the discovery and optimization of a series of RAF inhibitors with a novel spiro structure. The most potent spiro mol. 9 showed excellent in vitro potency against b/c RAF enzymes and RAS mutant H358 cancer cells with minimal paradoxical RAF signaling activation. Compound 9 also exhibited good drug-like properties as demonstrated by in vitro cytochrome P 450 (CYP), liver microsome stability (LMS) data and moderate oral pharmacokinetics (PK) profiles in rat and mouse.
Bioorganic & Medicinal Chemistry Letters published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (KRAS). 112253-70-0 belongs to class amides-buliding-blocks, and the molecular formula is C7H7BrN2O, Synthetic Route of 112253-70-0.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics