Synthesis and evaluation of 4-Anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade

Autor:	Karen Collins, Nan Zhang, Robert Mallon, Steven C. Kim, Allan Wissner, Carolyn Discafani, Dennis Powell, Constance Kohler, Jeremy I. Levin, Donald Wojciechowicz, Diane H. Boschelli, Dan Maarten Berger, Minu Dutia, Xuemei Du, Nancy Torres, Larry Feldberg, Biqi Wu, M. Brawner Floyd
Rok vydání:	2003
Předmět:	Stereochemistry Transplantation Heterologous Clinical Biochemistry MAP Kinase Kinase 1 Pharmaceutical Science Antineoplastic Agents Biochemistry Chemical synthesis Inhibitory Concentration 50 Mice Structure-Activity Relationship Cell Line Tumor Nitriles Drug Discovery Animals Humans Structure–activity relationship Enzyme Inhibitors Protein kinase A Molecular Biology Mitogen-Activated Protein Kinase Kinases biology Chemistry Kinase Organic Chemistry Neoplasms Experimental Transplantation Treatment Outcome Enzyme inhibitor Mitogen-activated protein kinase Quinolines biology.protein Molecular Medicine Signal transduction Cell Division Signal Transduction
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 13:3031-3034
ISSN:	0960-894X
Popis:	4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6,7-diethoxy-3-quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure-activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7348c798cec640b4049d2f270b74eb6d https://doi.org/10.1016/s0960-894x(03)00640-1 Zobrazit plný text záznamu Full Text from ScienceDirect