Ramurthy, Savithri published the artcileDesign and Discovery of N-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic, SDS of cas: 624734-19-6, the publication is Journal of Medicinal Chemistry (2020), 63(5), 2013-2027, database is CAplus and MEDLINE.
Direct pharmacol. inhibition of RAS has remained elusive, and efforts to target CRAF have been challenging due to the complex nature of RAF signaling, downstream of activated RAS, and the poor overall kinase selectivity of putative RAF inhibitors. Herein, we describe 15, a selective B/C RAF inhibitor, which was developed by focusing on drug-like properties and selectivity. Our previous tool compound, 3, was potent, selective, efficacious, and well tolerated in preclin. models, but the high human intrinsic clearance precluded further development and prompted further investigation of close analogs. A structure-based approach led to a pyridine series with an alc. side chain that could interact with the DFG loop and significantly improved cell potency. Further mitigation of human intrinsic clearance and time-dependent inhibition led to the discovery of 15. Due to its excellent properties, it was progressed through toxicol. studies and is being tested in phase 1 clin. trials.
Journal of Medicinal Chemistry published new progress about 624734-19-6. 624734-19-6 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Fluoride,Ketone, name is 3-Fluorodihydro-2H-pyran-4(3H)-one, and the molecular formula is C5H7FO2, SDS of cas: 624734-19-6.
Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics