1303469-70-6Relevant articles and documents
Pyrimidinopyrimidine inhibitors of ketohexokinase: Exploring the ring C2 group that interacts with Asp-27B in the ligand binding pocket
Maryanoff, Bruce E.,O'Neill, John C.,McComsey, David F.,Yabut, Stephen C.,Luci, Diane K.,Gibbs, Alan C.,Connelly, Margery A.
scheme or table, p. 5326 - 5329 (2012/09/07)
Inhibitors of ketohexokinase (KHK) have potential for the treatment of diabetes and obesity. We have continued studies on a pyrimidinopyrimidine series of potent KHK inhibitors by exploring the 2-position substituent (R 3) that interacts with Asp-27B in the ATP-binding region of KHK (viz. 1, 2; Table 1). We found that increased spacing between the terminal ammonium group and the heterocyclic scaffold (viz. 16-20), such that interaction with Asp-27B is not possible, still results in potent KHK inhibition (IC50 = 15-50 nM). We propose a new interaction with Asp-194, which serves to expand the pyrimidinopyrimidine pharmacophore.
Inhibitors of ketohexokinase: Discovery of pyrimidinopyrimidines with specific substitution that complements the ATP-binding site
Maryanoff, Bruce E.,O'Neill, John C.,McComsey, David F.,Yabut, Stephen C.,Luci, Diane K.,Jordan Jr., Alfonzo D.,Masucci, John A.,Jones, William J.,Abad, Marta C.,Gibbs, Alan C.,Petrounia, Ioanna
supporting information; experimental part, p. 538 - 543 (2011/09/15)
Attenuation of fructose metabolism by the inhibition of ketohexokinase (KHK; fructokinase) should reduce body weight, free fatty acids, and triglycerides, thereby offering a novel approach to treat diabetes and obesity in response to modern diets. We have
