Design and synthesis of alpha-aryloxy-alpha-methylhydrocinnamic acids: a novel class of dual peroxisome proliferator-activated receptor alpha/gamma agonists
| Autor: | Yanping, Xu, Christopher J, Rito, Garret J, Etgen, Robert J, Ardecky, James S, Bean, William R, Bensch, Jacob R, Bosley, Carol L, Broderick, Dawn A, Brooks, Samuel J, Dominianni, Patric J, Hahn, Sha, Liu, Dale E, Mais, Chahrzad, Montrose-Rafizadeh, Kathy M, Ogilvie, Brian A, Oldham, Mary, Peters, Deepa K, Rungta, Anthony J, Shuker, Gregory A, Stephenson, Allie E, Tripp, Sarah B, Wilson, Leonard L, Winneroski, Richard, Zink, Raymond F, Kauffman, James R, McCarthy |
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| Rok vydání: | 2004 |
| Předmět: |
Phenylpropionates
Receptors Cytoplasmic and Nuclear Hyperlipidemias Stereoisomerism Thiophenes Binding Competitive Cell Line Rats Rats Zucker Radioligand Assay Structure-Activity Relationship Diabetes Mellitus Type 2 Animals Humans Hypoglycemic Agents Female Hypolipidemic Agents Transcription Factors |
| Zdroj: | Journal of medicinal chemistry. 47(10) |
| ISSN: | 0022-2623 |
| Popis: | The design and synthesis of the dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist (S)-2-methyl-3-[4-[2-(5-methyl-2-thiophen-2-yl-oxazol-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid (2) for the treatment of type 2 diabetes and associated dyslipidemia are described. 2 possesses a potent dual hPPAR alpha/gamma agonist profile (IC(50) = 28 and 10 nM; EC(50) = 9 and 4 nM, respectively, for hPPARalpha and hPPARgamma). In preclinical models, 2 substantially improves insulin sensitivity and potently reverses diabetic hyperglycemia while significantly improving overall lipid homeostasis. |
| Databáze: | OpenAIRE |
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