2. Academic Validation
  3. 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 alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities

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 alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities

  • J Med Chem. 2005 Mar 24;48(6):2248-50. doi: 10.1021/jm0496436.
Pratik V Devasthale 1,  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
Affiliations

Affiliation

  • 1 Metabolic Diseases Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-5400, USA. pratik.devasthale@bms.com
PMID: 15771468 DOI: 10.1021/jm0496436
Abstract

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.

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