muraglitazar

{{short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 407806745

| IUPAC_name = N-[(4-Methoxyphenoxy)carbonyl]-N-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzyl}glycine

| image = Muraglitazar.svg

| width = 315

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status = Development terminated

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 331741-94-7

| ATC_prefix = None

| ATC_suffix =

| PubChem = 206044

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = W1MKM70WQI

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D05091

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 557580

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 178524

| C=29 | H=28 | N=2 | O=7

| smiles = CC1=C(N=C(O1)C2=CC=CC=C2)CCOC3=CC=C(C=C3)CN(CC(=O)O)C(=O)OC4=CC=C(C=C4)OC

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C29H28N2O7/c1-20-26(30-28(37-20)22-6-4-3-5-7-22)16-17-36-24-10-8-21(9-11-24)18-31(19-27(32)33)29(34)38-25-14-12-23(35-2)13-15-25/h3-15H,16-19H2,1-2H3,(H,32,33)

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = IRLWJILLXJGJTD-UHFFFAOYSA-N

| synonyms = 2-[(4-Methoxyphenoxy)carbonyl-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]amino]acetic acid

}}

Muraglitazar (proposed tradename Pargluva) is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ.{{cite journal | vauthors = Waites CR, Dominick MA, Sanderson TP, Schilling BE | title = Nonclinical safety evaluation of muraglitazar, a novel PPARalpha/gamma agonist | journal = Toxicological Sciences | volume = 100 | issue = 1 | pages = 248–58 | date = November 2007 | pmid = 17675651 | doi = 10.1093/toxsci/kfm193 | doi-access = free }}

The drug had completed phase III clinical trials,{{cite journal | vauthors = Kendall DM, Rubin CJ, Mohideen P, Ledeine JM, Belder R, Gross J, Norwood P, O'Mahony M, Sall K, Sloan G, Roberts A, Fiedorek FT, DeFronzo RA | display-authors = 6 | title = Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study | journal = Diabetes Care | volume = 29 | issue = 5 | pages = 1016–23 | date = May 2006 | pmid = 16644631 | doi = 10.2337/diacare.2951016 | url = http://care.diabetesjournals.org/content/diacare/29/5/1016.full.pdf | doi-access = free }} however in May 2006 Bristol-Myers Squibb announced that it had discontinued further development.{{cite web|title=Bristol-Myers Squibb Announces Discontinuation of Development of Muraglitazar, an Investigational Oral Treatment for Type 2 Diabetes|url=http://www.prnewswire.com/news-releases/bristol-myers-squibb-announces-discontinuation-of-development-of-muraglitazar-an-investigational-oral-treatment-for-type-2-diabetes-56462702.html|publisher=PR Newswire from Bristol-Myers Squibb|access-date=9 November 2016|date=May 18, 2006}}

Data on muraglitazar is relatively sparse due to the brief introduction and subsequent abandonment of this agent. One double-blind randomized clinical trial comparing muraglitazar and pioglitazone found that the effects of the former were favourable in terms of HDL-C increase, decrease in total cholesterol, apolipoprotein B, triglycerides and a greater reduction in HbA_1c (p <0.0001 for all comparisons). However, the muraglitazar group had a higher all-cause mortality, greater incidence of edema and heart failure and more weight gain compared to the pioglitazone group. A meta-analysis of the phase II and III clinical trials of muraglitazar revealed that it was associated with a greater incidence of myocardial infarction, stroke, transient ischemic attacks and congestive heart failure (CHF) when compared to placebo or pioglitazone.{{cite journal | vauthors = Nissen SE, Wolski K, Topol EJ | title = Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus | journal = JAMA | volume = 294 | issue = 20 | pages = 2581–6 | date = November 2005 | pmid = 16239637 | doi = 10.1001/jama.294.20.joc50147 | doi-access = }}