A series of analogs of vegfrecine, a natural quinone vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, was synthesized via oxidative amination of 2,5-dihydroxybenzamide with functionalized arylamine followed by ammonolysis and substitution of the quinone ring. The inhibitory activities of the analogs against the VEGFR-1 and -2 tyrosine kinases were assayed in vitro with the aim to identify a compound suitable to treat cancer and inflammatory diseases. Alterations of the functionality of the phenyl group, substitution of the quinone ring, and oxidative cyclization of the 1-carboxamide-2-aminoquinone moiety to form an isoxazole quinone ring were examined. Introduction of halo- and alkyl-substituents at the 5′-position of the phenyl ring resulted in potent inhibition of the VEGFR-1 and -2 tyrosine kinases. In particular, structural modification at C-5′ on the phenyl ring was shown to significantly affect the selectivity of the inhibition between the VEGFR-1 and -2 tyrosine kinases. Compound 8, 5′-methyl-vegfrecine, showed superior selectivity toward the VEGFR-2 tyrosine kinase over the VEGFR-1 tyrosine kinase.

一系列 vegfrecine 类似物是一种天然醌血管内皮生长因子受体 (VEGFR) 酪氨酸激酶抑制剂，通过 2,5-二羟基苯甲酰胺与官能化芳胺的氧化胺化，然后氨解和取代醌环合成。体外分析了类似物对 VEGFR-1 和 -2 酪氨酸激酶的抑制活性，目的是确定一种适合治疗癌症和炎症疾病的化合物。检查了苯基官能团的改变、醌环的取代和 1-甲酰胺-2-氨基醌部分的氧化环化以形成异恶唑醌环。在苯环的 5'-位引入卤素和烷基取代基导致对 VEGFR-1 和 -2 酪氨酸激酶的有效抑制。特别是，苯环上 C-5' 处的结构修饰显示出显着影响 VEGFR-1 和 -2 酪氨酸激酶之间抑制的选择性。化合物如图 8 所示，5'-甲基-vegfrecine 对 VEGFR-2 酪氨酸激酶显示出优于 VEGFR-1 酪氨酸激酶的选择性。