385836-94-2Relevant academic research and scientific papers
Novel glucagon receptor antagonists with improved selectivity over the glucose-dependent insulinotropic polypeptide receptor
Kodra, János T.,J?rgensen, Anker Steen,Andersen, Birgitte,Behrens, Carsten,Brand, Christian Lehn,Christensen, Inger Th?ger,Guldbrandt, Mette,Jeppesen, Claus Bekker,Knudsen, Lotte B.,Madsen, Peter,Nishimura, Erica,Sams, Christian,Sidelmann, Ulla G.,Pedersen, Raymon A.,Lynn, Francis C.,Lau, Jesper
experimental part, p. 5387 - 5396 (2009/07/01)
Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closely related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a >1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperglycemia in Sprague - Dawley rats. Furthermore, the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.
AMINO ACID DERIVATIVES
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Page/Page column 31, (2008/06/13)
The present invention relates to a method of treating pain using a compound of formula (I), wherein Ar, R1, R3 and R3a are as defined herein. The invention also relates to certain novel compounds of formula (I).
AMINO ACID DERIVATIVES
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Page/Page column 29-30, (2008/06/13)
The present invention relates to compounds of formula (I): wherein R1, R2, R4 and R4a are as defined herein. The invention also relates to the use of compounds of formula (I) for the treatment of pain.
Glucagon antagonists/inverse agonists
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, (2008/06/13)
A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism, such as dyslipidemia, and obesity.
