| Literature DB >> 31818630 |
Ronald J Hinklin1, Brian R Baer2, Steven A Boyd2, Mark D Chicarelli2, Kevin R Condroski2, Walter E DeWolf2, John Fischer2, Michele Frank2, Gary P Hingorani2, Patrice A Lee2, Nickolas A Neitzel2, Scott A Pratt2, Ajay Singh2, Francis X Sullivan2, Timothy Turner2, Walter C Voegtli2, Eli M Wallace2, Lance Williams2, Thomas D Aicher2.
Abstract
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.Entities:
Keywords: Diabetes; Glucokinase; Glucokinase activator; OGTT; S(0.5); Structure-aided design; Structure-based design; Type II diabetes; V(max); ob/ob mouse
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Year: 2019 PMID： 31818630 DOI： 10.1016/j.bmc.2019.115232
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641