Design and Synthesis of N-[(4-Methoxyphenoxy)carbonyl]-N-[[4-[2-(5- methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a Novel Peroxisome Proliferator-Activated Receptor α/γ Dual Agonist with Efficacious Glucose and Lipid-Lowering Activities

Autor:	Denis E. Ryono, Chen Sean, Pratik Devasthale, Shu Y Chang, John R. Wetterau, W. Griffith Humphreys, Gary J. Grover, Dennis Farrelly, Jeon Yoon T, Fucheng Qu, Ramakrishna Seethala, Narayanan Hariharan, Wei Wang, Zhengping Ma, Scott A. Biller, Rajasree Golla, Lisa Moore, Arthur M. Doweyko, Michael Cap, Fred Selan, Jimmy Ren, Paul G. Sleph, Hao Zhang, Aaron Tieman, Vito G. Sasseville, Thomas Harrity, Gamini Chandrasena, Chunning Shao, Peter T. W. Cheng, Lin Cheng, Wei Sun
Rok vydání:	2004
Předmět:	Blood Glucose Male Transcriptional Activation Agonist Stereochemistry medicine.drug_class medicine.medical_treatment Glycine Mice Obese Peroxisome proliferator-activated receptor Hyperlipidemias Chemical synthesis Cell Line Muraglitazar Mice Drug Discovery Adipocytes medicine Animals Humans Hypoglycemic Agents Insulin PPAR alpha Oxazoles Triglycerides Hypolipidemic Agents ADME chemistry.chemical_classification Chemistry Fatty Acids Biological activity PPAR gamma Diabetes Mellitus Type 2 Molecular Medicine
Zdroj:	Journal of Medicinal Chemistry. 48:2248-2250
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm0496436
Popis:	Muraglitazar/BMS-298585 (2) has been identified as a non-thiazolidinedione PPAR alpha/gamma dual agonist that shows potent activity in vitro at human PPARalpha (EC(50) = 320 nM) and PPARgamma(EC(50) = 110 nM). Compound 2 shows excellent efficacy for lowering glucose, insulin, triglycerides, and free fatty acids in genetically obese, severely diabetic db/db mice and has a favorable ADME profile. Compound 2 is currently in clinical development for the treatment of type 2 diabetes and dyslipidemia.
Databáze:	OpenAIRE
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