Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation and structure–activity relationships. Part 2

The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted phenyl groups, 4-[(methylamino)methyl]benzaldehyde (22) and 5-isoindolinecarbaldehyde (24) (6-tert-butylthieno[2,3-d]pyrimidin-4-yl)hydrazone derivatives have been identified. In this paper, the potency, selectivity profile and structure–activity relationships of our synthetic compounds are discussed.

The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as CDK4 inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted phenyl groups, 4-[(methylamino)methyl]benzaldehyde (6-tert-butylthieno[2,3-d]pyrimidin-4-yl)hydrazone and 5-isoindolinecarbaldehyde (6-tert-butylthieno[2,3-d]pyrimidin-4-yl)hydrazone have been identified. The potency, selectivity profile and structure–activity relationships of our compounds are discussed.Figure optionsDownload as PowerPoint slide