Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors

SGK1 inhibitors 1 and 2 suffered from poor oral exposure that could be attributed to factors such as high clearance and formation of glucuronic acid conjugates. Incorporation of appropriately-placed substituents was an effective means of reducing clearance and, in some cases, suppressing glucuronida...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-08, Vol.19 (15), p.4441-4445
Hauptverfasser:	Hammond, Marlys, Washburn, David G., Hoang, Tram H., Manns, Sharada, Frazee, James S., Nakamura, Hiroko, Patterson, Jaclyn R., Trizna, Walter, Wu, Charlene, Azzarano, Leonard M., Nagilla, Rakesh, Nord, Melanie, Trejo, Rebecca, Head, Martha S., Zhao, Baoguang, Smallwood, Angela M., Hightower, Kendra, Laping, Nicholas J., Schnackenberg, Christine G., Thompson, Scott K.
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Analytical, structural and metabolic biochemistry Animals BASIC BIOLOGICAL SCIENCES Biological and medical sciences Biological Availability Chemistry, Pharmaceutical - methods DESIGN Drug Design Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology Enzymes and enzyme inhibitors EXCRETION Fundamental and applied biological sciences. Psychology GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE Glucocorticoids - chemistry GLUCURONIC ACID Glucuronic Acid - chemistry Glucuronidation Immediate-Early Proteins - antagonists & inhibitors Immediate-Early Proteins - chemistry IN VIVO Inhibitory Concentration 50 Kinase inhibitor Medical sciences Miscellaneous Models, Chemical Molecular Conformation Pharmacology. Drug treatments PHOSPHOTRANSFERASES Protein Kinase Inhibitors - antagonists & inhibitors Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - chemistry Rats Serum and glucocorticoid-regulated kinase SGK1 Structure-Activity Relationship SYNTHESIS TESTING Transferases
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