Glucose-6-phosphatase catalytic enzyme inhibitors: synthesis and in vitro evaluation of novel 4, 5, 6, 7-tetrahydrothieno [3, 2-c]-and-[2, 3-c] pyridines

…, P Jakobsen, AR Varming, N Westergaard

Index: Madsen, Peter; Lundbeck, Jane M.; Jakobsen, Palle; Varming, Annemarie R.; Westergaard, Niels Bioorganic and Medicinal Chemistry, 2000 , vol. 8, # 9 p. 2277 - 2289

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Citation Number: 31

Abstract

The discovery of the first class of potent glucose-6-phosphatase catalytic site inhibitors, substituted 4, 5, 6, 7-tetrahydrothieno [3, 2-c]-and-[2, 3-c] pyridines, is described. Optimisation of this series involved solution phase combinatorial synthesis and very potent compounds were prepared with IC50 values down to 140 nM. The structure–activity relationship (SAR) of these compounds indicates that: a tetrahydrothieno [3, 2-c] pyridine ...