Research Area · Protein Kinase CK2

4-Aminothieno[2,3-d]pyrimidines

ATP-competitive CK2 inhibitors based on a heterocyclic scaffold amenable to systematic structural modification.

4-aminothieno[2,3-d]pyrimidine inhibitor bound within the ATP-binding pocket of protein kinase CK2

Novel CK2 inhibitors were identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in this study were 3-(5-p-tolylthieno[2,3-d]pyrimidin-4-ylamino)benzoic acid, 5e (NHTP23, IC50 = 0.01 mM); 3-(5-phenylthieno[2,3-d]pyrimidin-4-ylamino)benzoic acid, 5g (NHTP25, IC50 = 0.065 mM); and 3-(6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-ylamino)benzoic acid, 5n (NHTP33, IC50 = 0.008 mM). A binding mode for compounds of this class within the ATP-binding site of CK2 was proposed (Figure 1).

Proposed binding mode of NHTP33 within the active site of protein kinase CK2
Figure 1. Proposed binding mode of NHTP33 within the CK2 active site. Hydrogen bonds are shown as dashed lines.

Publication

Ostrynska OV, Balanda AO, Bdzhola VG, Golub AG, Kotey IM, Kukharenko OP, Gryshchenko AA, Briukhovetska NV, Yarmoluk SM. Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines. European Journal of Medicinal Chemistry. 2016;115:148–160.