Pyrido[3,4-g]quinazoline was previously identified as a relevant scaffold for protein kinase inhibition. In order to assess if the planarity of this heterocyclic system was essential to the protein kinase inhibitory potency observed in this series, new compounds were synthesized and evaluated, in which the central cycle was opened to provide (pyridin-4-yl)(pyrimidin-4-yl)methane derivatives, which were prepared from the corresponding ketone precursor. After preparing (2-aminopyrimidin-4-yl)(pyridin-4-yl)methanone, derivatives were synthesized and evaluated toward a panel of protein kinases. The results demonstrated that the planar pyrido[3,4-g]quinazoline tricyclic system was mandatory to maintain the protein kinase inhibitory potency in this series.

吡啶并[3,4- g ]喹唑啉先前被鉴定为蛋白激酶抑制的相关支架。为了评估该杂环系统的平面性是否对该系列中观察到的蛋白激酶抑制效力至关重要，合成并评估了新化合物，其中打开中央循环以提供(pyridin-4-yl)(pyrimidin- 4-基)甲烷衍生物，由相应的酮前体制备。制备(2-氨基嘧啶-4-基)(吡啶-4-基)甲酮后，合成衍生物并针对一组蛋白激酶进行评估。结果表明，平面吡啶并[3,4- g ]喹唑啉三环系统对于维持该系列中的蛋白激酶抑制效力是必需的。