期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 49, 期 26, 页码 7807-7815出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm060428u
关键词
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A series of novel, multisubstrate, bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase (TP) is described. Thymidine phosphorylase has been implicated in angiogenesis and plays a significant role in tumor progression and metastasis. The presence and orientation of the phosphonate moiety (acting as a phosphate mimic) in these derivatives were critical for inhibitory activity. The most active compounds possessed a phosphonate group in an endo orientation. This was consistent with molecular modeling results that showed the endo isomer protein-ligand complex to be lower in energy than the exo complex.
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