1293932-54-3

Upstream product

• 29632-74-4 2-fluro-4-iodoaniline 
• 848852-33-5 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-vinylbenzoic acid 
• 3279-95-6 O-(2-hydroxyethyl)hydroxylamine 
• 848852-32-4 2,3,4-trifluoro-5-vinylbenzoic acid 

Downstream Products

• 874100-39-7 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-formyl-N-(2-hydroxyethoxy)benzamide 
• 874100-40-0 5-[1,3]dioxolan-2-yl-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide 
• 1313037-46-5 C₁₉H₁₉F₃IN₃O₄S 
• 874100-62-6 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methoxyamino-methyl)-benzamide 
• 874100-89-7 C₂₀H₂₀F₃IN₄O₅ 
• 874101-00-5 CH4987655 

Relevant academic research and scientific papers

Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent

The MAP kinase pathway is one of the most important pathways involved in cell proliferation and differentiation, and its components are promising targets for antitumor drugs. Design and synthesis of a novel MEK inhibitor, based on the 3D-structural information of the target enzyme, and then multidimensional optimization including metabolic stability, physicochemical properties and safety profiles were effectively performed and led to the identification of a clinical candidate for an orally available potent MEK inhibitor, CH4987655, possessing a unique 3-oxo-oxazinane ring structure at the 5-position of the benzamide core structure. CH4987655 exhibits slow dissociation from the MEK enzyme, remarkable in vivo antitumor efficacy both in mono- and combination therapy, desirable metabolic stability, and insignificant MEK inhibition in mouse brain, implying few CNS-related side effects in human. An excellent PK profile and clear target inhibition in PBMC were demonstrated in a healthy volunteer clinical study.

NOVEL CRYSTAL FORM OF 3,4-DIFLUORO-2-(2-FLUORO-4-IODO-PHENYL AMINO)-N-(2-HYDROXY-ETHOXY)-5-(3-OXO-[1,2]OXAZINAN-2-YLMETHYL)-BENZAMIDE

PROBLEM TO BE SOLVED: To provide an active pharmaceutical ingredient that is useful as MEK inhibitors and is stable physicochemically. SOLUTION: The present invention provides an educt I-type crystal of 3,4-difluoro-2-(2-fluoro-4-iodo-phenyl amino)-n-(2-hydroxy-ethoxy)-5-(3-oxo-[1,2]oxazinan-2-ylmethyl)-benzamide, having peaks with diffraction angles expressed by 2θ of 14.9, 16.9 and 23.1° (±0.2°) in a powder X-ray diffraction pattern measured using Cu Kα(1.54060?) as an X-ray source. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT