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

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; T. W. Cheng, Peter

doi:10.1021/jm0496436.s001

jm0496436_si_001.pdf (112.97 kB)

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

journal contribution

posted on 2005-03-24, 00:00 authored by Pratik V. Devasthale, Sean Chen, Yoon Jeon, Fucheng Qu, Chunning Shao, Wei Wang, Hao Zhang, Michael Cap, Dennis Farrelly, Rajasree Golla, Gary Grover, Thomas Harrity, Zhengping Ma, Lisa Moore, Jimmy Ren, Ramakrishna Seethala, Lin Cheng, Paul Sleph, Wei Sun, Aaron Tieman, John R. Wetterau, Arthur Doweyko, Gamini Chandrasena, Shu Y. Chang, W. Griffith Humphreys, Vito G. Sasseville, Scott A. Biller, Denis E. Ryono, Fred Selan, Narayanan Hariharan, Peter T. W. Cheng

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 treatment of type 2 diabetes and dyslipidemia.