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 …

…, G Grover, T Harrity, Z Ma, L Moore, J Ren…

Index: Devasthale, Pratik V.; Chen, Sean; Jeon, Yoon; Qu, Fucheng; Shao, Chunning; Wang, Wei; Zhang, Hao; Cap, Michael; Farrelly, Dennis; Golla, Rajasree; Grover, Gary; Harrity, Thomas; Ma, Zhengping; Moore, Lisa; Ren, Jimmy; Seethala, Ramakrishna; Cheng, Lin; Sleph, Paul; Sun, Wei; Tieman, Aaron; Wetterau, John R.; Doweyko, Arthur; Chandrasena, Gamini; Chang, Shu Y.; Humphreys, W. Griffith; Sasseville, Vito G.; Biller, Scott A.; Ryono, Denis E.; Selan, Fred; Hariharan, Narayanan; Cheng, Peter T. W. Journal of Medicinal Chemistry, 2005 , vol. 48, # 6 p. 2248 - 2250

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Citation Number: 134

Abstract

Muraglitazar/BMS-298585 (2) has been identified as a non-thiazolidinedione PPAR α/γ dual agonist that shows potent activity in vitro at human PPARα (EC50= 320 nM) and PPARγ (EC50= 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 ...