The contribution of a 2-amino group on receptor tyrosine kinase inhibition and antiangiogenic activity in 4-anilinosubstituted pyrrolo[2,3-d]pyrimidines.
The contribution of a 2-amino group on receptor tyrosine kinase inhibition and antiangiogenic activity in 4-anilinosubstituted pyrrolo[2,3-d]pyrimidines.
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DOI：
10.1016/j.bmcl.2010.03.064
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发表时间：
2010-05-15
影响因子：
2.7
通讯作者：
Buchanan, Aaron
中科院分区：
文献类型：
--
作者：
Gangjee, Aleem;Namjoshi, Ojas A.;Ihnat, Michael A.;Buchanan, Aaron
我们比较了一系列具有和不具有2-氨基的吡咯[2,3-d]嘧啶，以确定我们的假设的有效性，即包含该基团可以提高抗受体酪氨酸激酶（RTK）的效力。与2-去氨基类似物相比，2-氨基类似物对表皮生长因子受体（EGFR）和血小板衍生生长因子-β (PDGFR-β)在全细胞抑制试验和A431细胞毒性试验中表现更好。然而，2-去氨基类似物对血管内皮生长因子-2 （VEGFR-2）的抑制作用比相应的2-氨基化合物更有效。此外，在绒毛膜尿囊膜（CAM）实验中，没有一种2-去氨基化合物表现出比标准物更好的抗血管生成活性，只是微摩尔抑制剂。本研究验证了我们最初的假设，即在吡咯[2,3-d]嘧啶中包含一个2-氨基可以改善多种RTK抑制和抗血管生成活性。
Comparison between a series of pyrrolo[2,3-d]pyrimidines with and without the 2-amino group is presented in order to determine the validity of our hypothesis that inclusion of this group improves potency against receptor tyrosine kinases (RTK). The 2-amino analogs were better against epidermal growth factor receptor (EGFR) and platelet derived growth factor-β (PDGFR-β) in whole cell inhibition assays and in the A431 cytotoxicity assay compared to the 2-desamino analogs. However, the 2-desamino analogs were more potent inhibitors against vascular endothelial growth factor-2 (VEGFR-2) than the corresponding 2-amino compounds. In addition, none of the 2-desamino compounds exhibited better anti-angiogenic activity in the chorioallantoic membrane (CAM) assay as compared to the standard and were only micromolar inhibitors. This study validates our original hypothesis that the inclusion of a 2-amino group in pyrrolo[2,3-d]pyrimidines improves multiple RTK inhibition and antiangiogenic activity.
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影响因子：
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