Total synthesis of antascomicin B.
Explore the source record for details and available documents.
Molecular Structure↗
Biomedical subjects
Kosuke Yasuda
Publications and source records attributed to Kosuke Yasuda.
Glucokinase-activating ureas.
The synthesis, SAR and biological evaluation of a series of ureas that activate glucokinase, a target for diabetes therapy as a result of its critical role in the regulation of whole-body glucose homeostasis, are described. Some of the urea-containing glucokinase activators lowered blood glucose levels in vivo following oral dosing to C57BL/6J mice.
Administration, Oral↗
Modifications and structure-activity relationships at the 2-position of 4-sulfonamidopyrimidine derivatives as potent endothelin antagonists.
To improve water solubility and to study structure-activity relationships, we modified the structure of the pyrimidine nucleus of each of a series of potent ET(A) antagonists, 3a and 4a, at the 2-position. In a previous study, each of these antagonists showed an extremely high affinity for the ET(A) receptor in porcine aortic membrane (IC(50) 3a; < 0.001 nM, 4a; 0.0039 nM). Two modification methods, one being the addition of organolithium followed by DDQ oxidation and the other being the nucleophilic substitution of 2-(methylsulfonyl)pyrimidine, were applied individually to synthesize 2-substituted-4-sulfonamidopyrimidine derivatives. The introduction of aryl, heteroaryl, alkyl, amino, alkoxy, or alkylthio groups into the 2-position varied the affinity. Derivatives with hydrophilic groups at the 2-position showed higher water solubility but tended to reduce the affinity for the ET(A) receptor.
Animals↗