Gazit A, App H, McMahon G, Chen J, Levitzki A, Bohmer F D
Department of Biological Chemistry, Alexander Silverman Institute of Life Science, Hebrew University of Jerusalem, Givat Ram, Israel.
J Med Chem. 1996 May 24;39(11):2170-7. doi: 10.1021/jm950727b.
A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups (methyl, methoxy) in the 6 and 7 positions and phenyl at the 3 position of quinoxalines and quinolines were essential for potency, in contrast to the hydrophilic catechol group in tyrphostins active against EGFR kinase inhibition at different sites. The inhibitors showed selectivity for PDGF and were not active against EGF receptor and HER-2/c-ErbB-2 receptor.
制备了一系列3-吲哚丙烯腈酪氨酸磷酸化抑制剂、2-氯-3-苯基喹啉和3-芳基喹喔啉，并测试了它们对血小板衍生生长因子受体酪氨酸激酶（PDGF-RTK）活性的抑制作用。发现抑制剂的效力顺序为喹喔啉>喹啉>吲哚。与在不同位点对表皮生长因子受体（EGFR）激酶抑制有活性的酪氨酸磷酸化抑制剂中的亲水性儿茶酚基团相反，喹喔啉和喹啉6位和7位的亲脂性基团（甲基、甲氧基）以及3位的苯基对效力至关重要。这些抑制剂对血小板衍生生长因子（PDGF）具有选择性，对表皮生长因子（EGF）受体和HER-2/c-ErbB-2受体无活性。
