Wei Linyi, Malhotra Sanjay V
Laboratory of Synthetic Chemistry, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Medchemcomm. 2012 Oct;3(10):1250-1257. doi: 10.1039/C2MD20097J.
A new series of 4-substituted 2-amino pyrido[3,4-]pyrimidine derivatives has been designed and synthesized as potential anticancer agents. These compounds were prepared from a common intermediate, 4-chloro-8-methoxy pyrido[3,4-]pyrimidin-2-amine, followed by palladium catalyzed cross-coupling reactions or nucleophilic aromatic substitutions at the C-4 position. Evaluation of the representative analogs using the US National Cancer Institute's 60 human cancer cell line (NCI 60) panel identified some of these compounds as exhibiting highly selective activities against breast cancer and renal cancer cell lines. A structure-activity relationship (SAR) study was explored to facilitate further development of this new class of compounds.
已设计并合成了一系列新的4-取代2-氨基吡啶并[3,4 -]嘧啶衍生物作为潜在的抗癌剂。这些化合物由常见中间体4-氯-8-甲氧基吡啶并[3,4 -]嘧啶-2-胺制备，随后通过钯催化的交叉偶联反应或在C-4位的亲核芳香取代反应。使用美国国立癌症研究所的60种人类癌细胞系（NCI 60）面板对代表性类似物进行评估，确定其中一些化合物对乳腺癌和肾癌细胞系表现出高度选择性活性。探索了构效关系（SAR）研究以促进这类新化合物的进一步开发。
