Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones
| Autor: | Raffaella Cincinelli, Sabrina Dallavalle, Giuliana Cassinelli, Giuditta Cuccuru, Raffaella Nannei, Cinzia Lanzi, Eleonora Rizzi, Franco Zunino |
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| Rok vydání: | 2007 |
| Předmět: |
Indoles
Blotting Western Clinical Biochemistry Pharmaceutical Science Biochemistry Mice Structure-Activity Relationship Growth factor receptor Drug Discovery Animals Protein kinase A Cytotoxicity Protein Kinase Inhibitors neoplasms Molecular Biology biology Kinase Chemistry Proto-Oncogene Proteins c-ret Organic Chemistry Cell culture Enzyme inhibitor NIH 3T3 Cells biology.protein Molecular Medicine Signal transduction Tyrosine kinase |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 17:3962-3968 |
| ISSN: | 0960-894X |
| Popis: | A novel series of 3-arylureidobenzylidene-indolin-2-ones was synthesized and their inhibitory activity against Ret tyrosine kinase investigated in comparison with the Ret inhibitor RPI-1 as a reference compound for this series. A few compounds were able to revert the RETC634R oncogene-transformed morphologic phenotype of NIH3T3MEN2A cells and showed a selective antiproliferative activity against these cells as compared to parental NIH3T3 cells or NIH3T3 cells transformed with a non-tyrosine kinase oncogene (NIH3T3H-RAS). Inhibition of Ret enzyme activity by effective derivatives was confirmed in a kinase assay. Structure–activity relationship indicated a favourable activity for 5,6-dimethoxyindolinone derivatives with H, OH, or OMe in the para position of the distal aryl ring. |
| Databáze: | OpenAIRE |
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