Bioorganic & medicinal chemistry, 2020-01, Vol.28 (1), p.115232-115232, Article 115232
- Hinklin, Ronald J.
- Baer, Brian R.
- Boyd, Steven A.
- Chicarelli, Mark D.
- Condroski, Kevin R.
- DeWolf, Walter E.
- Fischer, John
- Frank, Michele
- Hingorani, Gary P.
- Lee, Patrice A.
- Neitzel, Nickolas A.
- Pratt, Scott A.
- Singh, Ajay
- Sullivan, Francis X.
- Turner, Timothy
- Voegtli, Walter C.
- Wallace, Eli M.
- Williams, Lance
- Aicher, Thomas D.
2020
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Hinklin, Ronald J.
- Baer, Brian R.
- Boyd, Steven A.
- Chicarelli, Mark D.
- Condroski, Kevin R.
- DeWolf, Walter E.
- Fischer, John
- Frank, Michele
- Hingorani, Gary P.
- Lee, Patrice A.
- Neitzel, Nickolas A.
- Pratt, Scott A.
- Singh, Ajay
- Sullivan, Francis X.
- Turner, Timothy
- Voegtli, Walter C.
- Wallace, Eli M.
- Williams, Lance
- Aicher, Thomas D.
- Titel
- Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator
- Ist Teil von
- Bioorganic & medicinal chemistry, 2020-01, Vol.28 (1), p.115232-115232, Article 115232
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- [Display omitted] Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 72 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0968-0896eISSN: 1464-3391DOI: 10.1016/j.bmc.2019.115232Titel-ID: cdi_proquest_miscellaneous_2323480523
- Format
- –
- Schlagworte
- Animals, Binding Sites, Blood Glucose - analysis, Crystallography, X-Ray, Diabetes, Diabetes Mellitus, Experimental - drug therapy, Diabetes Mellitus, Experimental - metabolism, Diabetes Mellitus, Experimental - pathology, Drug Design, Drug Evaluation, Preclinical, Enzyme Activators - chemistry, Enzyme Activators - metabolism, Enzyme Activators - therapeutic use, Glucokinase, Glucokinase - chemistry, Glucokinase - metabolism, Glucokinase activator, Glucose Tolerance Test, Hypoglycemic Agents - chemistry, Hypoglycemic Agents - metabolism, Hypoglycemic Agents - therapeutic use, Kinetics, Mice, Mice, Inbred C57BL, Molecular Dynamics Simulation, ob/ob mouse, OGTT, S0.5, Structure-Activity Relationship, Structure-aided design, Structure-based design, Thiadiazoles - chemistry, Thiadiazoles - metabolism, Type II diabetes, Vmax