Abstract
The design and synthesis of a novel class of 7-azaspiro[3.5]nonane GPR119 agonists are described. In this series, optimization of the right piperidine N-capping group (R2) and the left aryl group (R3) led to the identification of compound 54g as a potent GPR119 agonist. Compound 54g showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose lowering effect in diabetic rats.
Copyright © 2018 Elsevier Ltd. All rights reserved.
MeSH terms
-
Alkanes / chemical synthesis
-
Alkanes / chemistry*
-
Alkanes / pharmacokinetics
-
Animals
-
Blood Glucose / analysis
-
Cell Line
-
Diabetes Mellitus, Experimental / drug therapy
-
Diabetes Mellitus, Experimental / pathology
-
Drug Design*
-
Glucose Tolerance Test
-
Half-Life
-
Humans
-
Hypoglycemic Agents / chemical synthesis
-
Hypoglycemic Agents / chemistry
-
Hypoglycemic Agents / therapeutic use
-
Microsomes, Liver / metabolism
-
Piperidines / chemistry
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, G-Protein-Coupled / agonists*
-
Receptors, G-Protein-Coupled / metabolism
-
Structure-Activity Relationship
Substances
-
Alkanes
-
Blood Glucose
-
GPR119 protein, human
-
Hypoglycemic Agents
-
Piperidines
-
Receptors, G-Protein-Coupled
-
piperidine
-
nonane