Discovery of the oxazabicyclo[3.3.1]nonane derivatives as potent and orally active GPR119 agonists
| Autor: | Xiaoying Xu, Timothy J. Kowalski, William J. Greenlee, Hong Liu, Andrew Stamford, Brian Hawes, Xing Dai, Morgan Woods, Huadong Tang, Bernard R. Neustadt, Kim O’Neill, Hana Baker, Jingsong Hao |
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| Rok vydání: | 2015 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Biochemistry Receptors G-Protein-Coupled chemistry.chemical_compound Mice In vivo Drug Discovery medicine Animals Humans Hypoglycemic Agents Oral glucose tolerance Solubility Molecular Biology Octane Glucose tolerance test medicine.diagnostic_test Organic Chemistry Glucose Tolerance Test GPR119 Orally active HEK293 Cells Pyrimidines chemistry Molecular Medicine Nonane Azabicyclo Compounds |
| Zdroj: | Bioorganicmedicinal chemistry letters. 25(22) |
| ISSN: | 1464-3405 |
| Popis: | The design and synthesis of two conformationally restricted oxazabicyclo octane derivatives as GRP119 agonists is described. Derivatives of scaffold C, with syn configuration, have the best overall profiles with respect to solubility and in vivo efficacy. Compound 25a was found to have extremely potent agonistic activity and was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test at a dose of 0.1 mg/kg. |
| Databáze: | OpenAIRE |
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