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Modified 3-alkyl-1,8-dibenzylxanthines as GTP-competitive inhibitors of phosphoenolpyruvate carboxykinase.

Abstract：

:The first non-substrate like inhibitors of human cytosolic phosphoenolpyruvate carboxykinase (PEPCK) competitive with GTP are reported. An effort to discover orally active compounds that improve glucose homeostasis in Type 2 diabetics by reversibly inhibiting PEPCK led to the discovery of 1-allyl-3-butyl-8-methylxanthine (5). We now report modifications at N-1 and C-8 that improved the in vitro activity of the initial xanthine HTS hit by 100-fold and a developing SAR for this class of inhibitor.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Foley LH,Wang P,Dunten P,Ramsey G,Gubler ML,Wertheimer SJ

doi

10.1016/s0960-894x(03)00722-4

subject

Has Abstract

pub_date

2003-10-20 00:00:00

pages

3607-10

issue

20

eissn

0960-894X

issn

1464-3405

pii

S0960894X03007224

journal_volume

13

pub_type

杂志文章

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