Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter

被引:95
作者
Song, XQ
Vig, BS
Lorenzi, PL
Drach, JC
Townsend, LB
Amidon, GL [1 ]
机构
[1] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA
关键词
D O I
10.1021/jm049450i
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [H-3]glycylsarcosine (Gly-Sar) uptake in HeLa/hPEPT1 cells by the amino acid ester prodrugs of BDCRB suggested their 2- to 4-fold higher affinity for hPEPT1 compared to BDCRB. Further, promoieties with hydrophobic side chains and L-configuration were preferred by the hPEPT1 transporter.
引用
收藏
页码:1274 / 1277
页数:4
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