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

作者：Pierre Fabrice^*; O'Brien Sean E; Haddach Mustapha; Bourbon Pauline; Schwaebe Michael K; Stefan Eric; Darjania Levan; Stansfield Ryan; Ho Caroline; Siddiqui Jain Adam; Streiner Nicole; Rice William G; Anderes Kenna; Ryckman David M

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(6): 1687-1691.

DOI：10.1016/j.bmcl.2011.01.091

• CK2
• Kinase inhibitor
• HIV
• Inflammation Pain

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.

• 出版日期2011-3-15