1243414-76-7Relevant academic research and scientific papers
Pyrimidone-based series of glucokinase activators with alternative donor-acceptor motif
Filipski, Kevin J.,Guzman-Perez, Angel,Bian, Jianwei,Perreault, Christian,Aspnes, Gary E.,Didiuk, Mary T.,Dow, Robert L.,Hank, Richard F.,Jones, Christopher S.,Maguire, Robert J.,Tu, Meihua,Zeng, Dongxiang,Liu, Shenping,Knafels, John D.,Litchfield, John,Atkinson, Karen,Derksen, David R.,Bourbonais, Francis,Gajiwala, Ketan S.,Hickey, Michael,Johnson, Theodore O.,Humphries, Paul S.,Pfefferkorn, Jeffrey A.
, p. 4571 - 4578 (2013)
Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond.
2-(3,5-DISUBSTITUTEDPHENYL)PYRIMIDIN-4(3H)-ONE DERIVATIVES
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Page/Page column 49-50, (2012/01/06)
O N NH R3 R2 O R1 168 ABSTRACT The present invention provides a 2-(3,5-disubstitutedphenyl)pyrimidin- 4(3H)-one compound of Formula (I) 5 (I) or a pharmaceutically acceptable salt thereof wherein R 1, R2 and R3 are as defined herein. The compounds of Formula (I) have been found to act as glucokinase activators. Consequently, the compounds of Formula (I) and 10 the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucokinase.
