Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy
Journal Article
·
· Bioorg. Med. Chem. Lett.
Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1005616
- Journal Information:
- Bioorg. Med. Chem. Lett., Vol. 19, Issue (4) ; 02, 2009; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Anthranilimide-based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes: 1. Identification of 1-amino-1-cycloalkyl carboxylic acid headgroups
Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa
Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor
Journal Article
·
Fri May 15 00:00:00 EDT 2009
· Bioorg. Med. Chem. Lett.
·
OSTI ID:1005616
+13 more
Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa
Journal Article
·
Mon Mar 08 00:00:00 EST 2010
· J. Med. Chem.
·
OSTI ID:1005616
+11 more
Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor
Journal Article
·
Mon Jun 21 00:00:00 EDT 2010
· J. Med. Chem.
·
OSTI ID:1005616
+20 more