203916-59-0Relevant articles and documents
Halogen Bonding Directed Supramolecular Quadruple and Double Helices from Hydrogen-Bonded Arylamide Foldamers
Liu, Chuan-Zhi,Koppireddi, Satish,Wang, Hui,Zhang, Dan-Wei,Li, Zhan-Ting
, p. 226 - 230 (2019)
Halogen bonding has been used to glue together hydrogen-bonded short arylamide foldamers to achieve new supramolecular double and quadruple helices in the solid state. Three compounds, which bear a pyridine at one end and either a CF2I or fluor
Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent
Isshiki, Yoshiaki,Kohchi, Yasunori,Iikura, Hitoshi,Matsubara, Yasuaki,Asoh, Kohsuke,Murata, Takeshi,Kohchi, Masami,Mizuguchi, Eisaku,Tsujii, Shinji,Hattori, Kazuo,Miura, Takaaki,Yoshimura, Yasushi,Aida, Satoshi,Miwa, Masanori,Saitoh, Ryoichi,Murao, Naoaki,Okabe, Hisafumi,Belunis, Charles,Janson, Cheryl,Lukacs, Christine,Schück, Verena,Shimma, Nobuo
scheme or table, p. 1795 - 1801 (2011/05/11)
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.
5-SUBSTITUTED-2-PHENYLAMINO-BENZAMIDE AS MEK INHIBITOR
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Page/Page column 73, (2008/06/13)
An objective of the present invention is to provide compounds that exhibit strong MEK-inhibiting activity and are stable in vivo and soluble in water, which can be used as preventive or therapeutic agents for proliferative diseases. The compounds of the present invention and pharmaceutically acceptable salts thereof are represented by the following formula (1): [where R1, R2, R3, R4, and X are the same as defined in the present patent application].