Design and evaluation of a 2-(2,3,6-trifluorophenyl)acetamide derivative as an agonist of the GPR119 receptor

The design and synthesis of a GPR119 agonist bearing a 2-(2,3,6-trifluorophenyl)acetamide group is described. The design capitalized on the conformational restriction found in N-β-fluoroethylamide derivatives to help maintain good levels of potency while driving down both lipophilicity and oxidative...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (5), p.1306-1309
Hauptverfasser:	Mascitti, Vincent, Stevens, Benjamin D., Choi, Chulho, McClure, Kim F., Guimarães, Cristiano R.W., Farley, Kathleen A., Munchhof, Michael J., Robinson, Ralph P., Futatsugi, Kentaro, Lavergne, Sophie Y., Lefker, Bruce A., Cornelius, Peter, Bonin, Paul D., Kalgutkar, Amit S., Sharma, Raman, Chen, Yue
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetamides - chemical synthesis Acetamides - chemistry Acetamides - pharmacology aerobiosis agonists Biological and medical sciences Configurational entropy Diabetes Drug Design Gauche effect General and cellular metabolism. Vitamins GPR119 Humans hydrophobicity Inhibitory Concentration 50 liver microsomes Magnetic Resonance Spectroscopy Medical sciences Metabolism Molecular Structure Pharmacology. Drug treatments Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - chemistry
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Zusammenfassung:	The design and synthesis of a GPR119 agonist bearing a 2-(2,3,6-trifluorophenyl)acetamide group is described. The design capitalized on the conformational restriction found in N-β-fluoroethylamide derivatives to help maintain good levels of potency while driving down both lipophilicity and oxidative metabolism in human liver microsomes. The chemical stability and bioactivation potential are discussed.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.01.088