Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties
| Autor: | Mustapha Haddach, Nicole Streiner, Caroline B. Ho, David M. Ryckman, Eric Stefan, William G. Rice, Fabrice Pierre, Kenna Anderes, Adam Siddiqui-Jain, Levan Darjania, Michael K. Schwaebe, Sean O'Brien, Pauline Bourbon, Ryan Stansfield |
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| Rok vydání: | 2010 |
| Předmět: |
animal structures
Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis Antiviral Agents chemistry.chemical_compound Structure-Activity Relationship In vivo Drug Discovery Structure–activity relationship Enzyme Inhibitors Casein Kinase II Molecular Biology chemistry.chemical_classification Analgesics fungi Organic Chemistry Quinoline Biological activity Hydrogen Bonding Enzyme chemistry embryonic structures Quinolines Molecular Medicine Casein kinase 2 Signal transduction |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(6) |
| ISSN: | 1464-3405 |
| Popis: | We describe the discovery of novel potent substituted pyrimido[4,5-c]quinoline ATP-competitive inhibitors of protein kinase CK2. A binding model of the inhibitors with the protein was elaborated on the basis of SAR and revealed various modes of interaction with the hinge region. Representative analog 14k (CK2 IC(50)=9 nM) showed anti-viral activity at nanomolar concentrations against HIV-1. Orally available compound 7e (CK2 IC(50)=3 nM) reduced pain in the phase II of a murine formalin model. These preliminary data confirm that properly optimized CK2 inhibitors may be used for anti-viral and pain therapy. |
| Databáze: | OpenAIRE |
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