Design and synthesis of certain 7-Aryl-2-Methyl-3-Substituted Pyrazolo{1,5-a}Pyrimidines as multikinase inhibitors

Recent Advances in the Discovery of CK2 Inhibitors

“…Additionally, different aryl substituents were introduced at position 7 to occupy the hydrophobic pocket and to augment the hydrophobic interactions around the hinge region. 95 The most active compound on CK2α was the oxadiazole derivative 48 ( Figure 38 ) with IC 50 = 0.093 μM. This compound also showed high inhibitory activity on TrkA, ALK2, c-KIT, EGFR, PIM1, CHK1, and CDK2 in submicromolar concentrations.…”

“…This compound also showed high inhibitory activity on TrkA, ALK2, c-KIT, EGFR, PIM1, CHK1, and CDK2 in submicromolar concentrations. Compound 10e exhibited antitumor activity against MCF7, HCT116, and EKVX cell lines and arrested the cell cycle in the G1/S phase and G1 phase in MCF7 and HCT116 cells …”

“…Recently, in 2023, Al-Qadhi et al used proper substitution and insertion strategies around pyrazolo­[1,5- a ]­pyrimidine scaffold to develop multitarget kinase inhibitors . The rationale of this work was based on the structures of the CDK2 and CHK1 inhibitors Dinaciclib and SCH900776.…”

“…The pyrazolo­[1,5- a ]­pyrimidine core was kept as a hinge binding moiety to take the place of adenine in the ATP binding pocket; then structural modifications were carried out around this scaffold by the proper selection of different pharmacophoric substituents at position 3 (carbonitrile, carboxamide, amidoxime, and 1,2,4-oxadiazole). Additionally, different aryl substituents were introduced at position 7 to occupy the hydrophobic pocket and to augment the hydrophobic interactions around the hinge region . The most active compound on CK2α was the oxadiazole derivative 48 (Figure ) with IC 50 = 0.093 μM.…”

“…Recently, in 2023, Al-Qadhi et al used proper substitution and insertion strategies around pyrazolo[1,5- a ]pyrimidine scaffold to develop multitarget kinase inhibitors. 95 The rationale of this work was based on the structures of the CDK2 and CHK1 inhibitors Dinaciclib and SCH900776. The pyrazolo[1,5- a ]pyrimidine core was kept as a hinge binding moiety to take the place of adenine in the ATP binding pocket; then structural modifications were carried out around this scaffold by the proper selection of different pharmacophoric substituents at position 3 (carbonitrile, carboxamide, amidoxime, and 1,2,4-oxadiazole).…”