title: 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.
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.
authors.affiliation: Metabolic Diseases Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-5400, USA. pratik.devasthale@bms.com
authors.forename: Pratik V
authors.initials: PV
authors.lastname: Devasthale
authors.forename: Sean
authors.initials: S
authors.lastname: Chen
authors.forename: Yoon
authors.initials: Y
authors.lastname: Jeon
authors.forename: Fucheng
authors.initials: F
authors.lastname: Qu
authors.forename: Chunning
authors.initials: C
authors.lastname: Shao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Cap
authors.forename: Dennis
authors.initials: D
authors.lastname: Farrelly
authors.forename: Rajasree
authors.initials: R
authors.lastname: Golla
authors.forename: Gary
authors.initials: G
authors.lastname: Grover
authors.forename: Thomas
authors.initials: T
authors.lastname: Harrity
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Ma
authors.forename: Lisa
authors.initials: L
authors.lastname: Moore
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ren
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Seethala
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Paul
authors.initials: P
authors.lastname: Sleph
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Aaron
authors.initials: A
authors.lastname: Tieman
authors.forename: John R
authors.initials: JR
authors.lastname: Wetterau
authors.forename: Arthur
authors.initials: A
authors.lastname: Doweyko
authors.forename: Gamini
authors.initials: G
authors.lastname: Chandrasena
authors.forename: Shu Y
authors.initials: SY
authors.lastname: Chang
authors.forename: W Griffith
authors.initials: WG
authors.lastname: Humphreys
authors.forename: Vito G
authors.initials: VG
authors.lastname: Sasseville
authors.forename: Scott A
authors.initials: SA
authors.lastname: Biller
authors.forename: Denis E
authors.initials: DE
authors.lastname: Ryono
authors.forename: Fred
authors.initials: F
authors.lastname: Selan
authors.forename: Narayanan
authors.initials: N
authors.lastname: Hariharan
authors.forename: Peter T W
authors.initials: PT
authors.lastname: Cheng
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005227:Fatty Acids / Q000097:blood; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008820:Mice, Obese; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D015533:Transcriptional Activation; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D014280:Triglycerides; D005998:Glycine; C500085:muraglitazar