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Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4- b ][1,4]oxazine derivatives as potent GPR 119 agonists.
- Source :
-
Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2020 Dec; Vol. 35 (1), pp. 50-58. - Publication Year :
- 2020
-
Abstract
- GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4- b ][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC <subscript>50</subscript> values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC <subscript>0-2h</subscript> at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).
- Subjects :
- Animals
Blood Glucose drug effects
Dose-Response Relationship, Drug
Glucose Tolerance Test
Humans
Hypoglycemic Agents chemical synthesis
Hypoglycemic Agents chemistry
Mice
Mice, Inbred C57BL
Molecular Structure
Oxazines chemical synthesis
Oxazines chemistry
Pyrimidines chemical synthesis
Pyrimidines chemistry
Structure-Activity Relationship
Hypoglycemic Agents pharmacology
Oxazines pharmacology
Pyrimidines pharmacology
Receptors, G-Protein-Coupled agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1475-6374
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of enzyme inhibition and medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31656107
- Full Text :
- https://doi.org/10.1080/14756366.2019.1681988