Synthesis of pyrazolo[4,3-a]phenanthridines, a new scaffold for Pim kinase inhibition
| Autor: | Pascale Moreau, Francis Giraud, Lionel Nauton, Laurent Gavara, Virginie Suchaud, Fabrice Anizon, Vincent Théry |
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| Přispěvatelé: | Institut de Chimie de Clermont-Ferrand (ICCF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Scaffold Molecular model Stereochemistry Clinical Biochemistry Pharmaceutical Science 010402 general chemistry 01 natural sciences Biochemistry Structure-Activity Relationship Proto-Oncogene Proteins c-pim-1 Pyrazolo[4 Cell Line Tumor hemic and lymphatic diseases Drug Discovery [CHIM]Chemical Sciences Humans Structure–activity relationship Protein Kinase Inhibitors Molecular Biology Cell Proliferation Pim kinases Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Cell growth Kinase Chemistry Organic Chemistry Combinatorial chemistry Phenanthridines 0104 chemical sciences Kinase inhibitors 3-a]phenanthridines Nitro In vitro antiproliferative activities Pyrazoles Molecular Medicine |
| Zdroj: | Bioorganic and Medicinal Chemistry Bioorganic and Medicinal Chemistry, Elsevier, 2014, 22, pp.4704-4710. ⟨10.1016/j.bmc.2014.07.011⟩ Bioorganic and Medicinal Chemistry, 2014, 22, pp.4704-4710. ⟨10.1016/j.bmc.2014.07.011⟩ |
| ISSN: | 0968-0896 1464-3391 |
| DOI: | 10.1016/j.bmc.2014.07.011 |
| Popis: | International audience; A new series of nitro or amino substituted pyrazolo[4,3-a]phenanthridines was synthesized in 6 steps from 5-bromo-6-nitroindazole. The evaluation of their inhibitory potency toward Pim kinases demonstrated that the nitro series could be considered as an interesting starting point for the development of new Pim kinase inhibitors, especially Pim-3. A preferential binding mode was suggested by molecular modeling experiments for nitro series and Pim-1/Pim-3 ATP-binding sites. Moreover, the most active compounds exhibited antiproliferative activities toward PC3 cells in the micromolar range. |
| Databáze: | OpenAIRE |
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