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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 04期

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

页码：1274 / 1277

页数：4

共 34 条

[1] Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir [J].