1361220-79-2Relevant academic research and scientific papers
Small molecule disruptors of the Glucokinase-Glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles
St. Jean, David J.,Ashton, Kate S.,Bartberger, Michael D.,Chen, Jie,Chmait, Samer,Cupples, Rod,Galbreath, Elizabeth,Helmering, Joan,Hong, Fang-Tsao,Jordan, Steven R.,Liu, Longbin,Kunz, Roxanne K.,Michelsen, Klaus,Nishimura, Nobuko,Pennington, Lewis D.,Poon, Steve F.,Reid, Darren,Sivits, Glenn,Stec, Markian M.,Tadesse, Seifu,Tamayo, Nuria,Van, Gwyneth,Yang, Kevin C.,Zhang, Jiandong,Norman, Mark H.,Fotsch, Christopher,Lloyd, David J.,Hale, Clarence
, p. 325 - 338 (2014/02/14)
In the previous report, we described the discovery and optimization of novel small molecule disruptors of the GK-GKRP interaction culminating in the identification of 1 (AMG-1694). Although this analogue possessed excellent in vitro potency and was a useful tool compound in initial proof-of-concept experiments, high metabolic turnover limited its advancement. Guided by a combination of metabolite identification and structure-based design, we have successfully discovered a potent and metabolically stable GK-GKRP disruptor (27, AMG-3969). When administered to db/db mice, this compound demonstrated a robust pharmacodynamic response (GK translocation) as well as statistically significant dose-dependent reductions in fed blood glucose levels.
SULFONYLPIPERAZINE DERIVATIVES THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN FOR THE TREATMENT OF DIABETES
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Page/Page column 348- 350, (2012/03/26)
The present invention relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
