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

…, P Wang, P Dunten, G Ramsey, ML Gubler…

Index: Foley, Louise H.; Wang, Ping; Dunten, Pete; Ramsey, Gwendolyn; Gubler, Mary-Lou; Wertheimer, Stanley J. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 20 p. 3607 - 3610

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Citation Number: 17

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 ...