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 Lettjournal_title
ACS medicinal chemistry lettersauthors
Tatani K,Hiratochi M,Nonaka Y,Isaji M,Shuto Sdoi
10.1021/ml500343rsubject
Has Abstractpub_date
2015-01-28 00:00:00pages
244-8issue
3issn
1948-5875journal_volume
6pub_type
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