2. Academic Validation
  3. Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties

Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties

  • Bioorg Med Chem Lett. 2011 Mar 15;21(6):1687-91. doi: 10.1016/j.bmcl.2011.01.091.
Fabrice Pierre 1,  Sean E O'Brien,  Mustapha Haddach,  Pauline Bourbon,  Michael K Schwaebe,  Eric Stefan,  Levan Darjania,  Ryan Stansfield,  Caroline Ho,  Adam Siddiqui-Jain,  Nicole Streiner,  William G Rice,  Kenna Anderes,  David M Ryckman
Affiliations

Affiliation

PMID: 21316963 DOI: 10.1016/j.bmcl.2011.01.091
Abstract

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.

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