抗血管生成吡咯基亚甲基氧化吲哚前药的合成与评价
Synthesis and evaluation of prodrugs for anti-angiogenic pyrrolylmethylidenyl oxindoles.
作者信息
Maskell Lesley, Blanche Emilie A, Colucci Marie A, Whatmore Jacqueline L, Moody Christopher J
机构信息
Peninsula Medical School, St. Luke's Campus, Exeter EX1 2LU, UK.
出版信息
Bioorg Med Chem Lett. 2007 Mar 15;17(6):1575-8. doi: 10.1016/j.bmcl.2006.12.108. Epub 2007 Jan 8.
Potential prodrugs of inhibitors of VEGF-induced angiogenesis have been investigated. The prodrug systems studied were the 4-nitrobenzyl, 2-nitrophenylacetyl and 3-methyl-3-(3,6-dimethylbenzo-1,4-quinon-2-yl)butanoyl groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The anti-angiogenic compounds studied were the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its novel 6-hydroxy derivative. The potentially pro-anti-angiogenic compounds were assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents.
已对血管内皮生长因子（VEGF）诱导血管生成抑制剂的潜在前药进行了研究。所研究的前药系统为4-硝基苄基、2-硝基苯乙酰基和3-甲基-3-(3,6-二甲基苯并-1,4-醌-2-基)丁酰基，它们易于连接到药物分子中的酸性羟基或氨基上，并在生物还原激活后释放。所研究的抗血管生成化合物为吡咯基亚甲基异吲哚酮SU5416（司马沙尼）及其新型6-羟基衍生物。与游离药物相比，对这些潜在的促抗血管生成化合物阻断人脐静脉内皮细胞（HUVECS）中VEGF诱导血管生成的能力进行了测定。
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