Identification of 8-aminoadenosine derivatives as a new class of human concentrative nucleoside transporter 2 inhibitors.

Abstract:

:Purine-rich foods have long been suspected as a major cause of hyperuricemia. We hypothesized that inhibition of human concentrative nucleoside transporter 2 (hCNT2) would suppress increases in serum urate levels derived from dietary purines. To test this hypothesis, the development of potent hCNT2 inhibitors was required. By modifying adenosine, an hCNT2 substrate, we successfully identified 8-aminoadenosine derivatives as a new class of hCNT2 inhibitors. Compound 12 moderately inhibited hCNT2 (IC50 = 52 ± 3.8 μM), and subsequent structure-activity relationship studies led to the discovery of compound 48 (IC50 = 0.64 ± 0.19 μM). Here we describe significant findings about structural requirements of 8-aminoadenosine derivatives for exhibiting potent hCNT2 inhibitory activity.

journal_name

ACS Med Chem Lett

authors

Tatani K,Hiratochi M,Nonaka Y,Isaji M,Shuto S

doi

10.1021/ml500343r

subject

Has Abstract

pub_date

2015-01-28 00:00:00

pages

244-8

issue

3

issn

1948-5875

journal_volume

6

pub_type

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