[EN] ARYLAMIDE COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, AND PREPARATION METHOD THEREFOR AND USE THEREOF [FR] COMPOSÉ ARYLAMIDE, COMPOSITION PHARMACEUTIQUE LE COMPRENANT, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION [ZH] 芳基酰胺化合物、包含其的药物组合物及其制备方法和用途
Isoindole-imide compounds and compositions comprising and methods of using the same
申请人:Muller W. George
公开号:US20070049618A1
公开(公告)日:2007-03-01
This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
ISOINDOLE-IMIDE COMPOUNDS AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
申请人:MULLER George W.
公开号:US20110144158A1
公开(公告)日:2011-06-16
This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
The present invention encompasses compounds of general formula (1)
wherein
R1 to R5 are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.
A series of novel VEGFR-2 inhibitors containing oxime as hinge binding fragment were described. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bond was employed to mimic the planar quinazoline. The oxime group was firstly introduced to interact with hinge region of VEGFR-2. Most of compounds tested showed moderate to high VEGFR-2 inhibitory activity. In particular, 121, 12p and 12y exhibited significant enzymatic inhibitory activity as well as potent antiproliferative activity against cancer cells. Molecular docking suggested that the salicylaldoxime formed two hydrogen bonds with hinge region. These biphenylureas could serve as promising lead compounds for developing novel anticancer agents. (C) 2014 Elsevier Masson SAS. All rights reserved.