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

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.