Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

The Journey of Thiazolidinediones as Modulators of PPARs for the Management of Diabetes: A Current Perspective

Author(s): Waquar Ahsan*

Volume 25, Issue 23, 2019

Page: [2540 - 2554] Pages: 15

DOI: 10.2174/1381612825666190716094852

Price: $65

Abstract

Peroxisome Proliferator-Activated Receptors (PPARs) also known as glitazone receptors are a family of receptors that regulate the expression of genes and have an essential role in carbohydrate, lipid and protein metabolism apart from other functions. PPARs come in 3 sub-types: PPAR-α, PPAR-β/δ and PPAR-γ - with PPAR-γ having 2 isoforms - γ1 and γ2. Upon activation, the PPARs regulate the transcription of various genes involved in lipid and glucose metabolism, adipocyte differentiation, increasing insulin sensitivity, prevention of oxidative stress and to a certain extent, modulation of immune responses via macrophages that have been implicated in the pathogenesis of insulin resistance. Hence, PPARs are an attractive molecular target for designing new anti-diabetic drugs. This has led to a boost in the research efforts directed towards designing of PPAR ligands - particularly ones that can selectively and specifically activate one or more of the PPAR subtypes. Though, PPAR- γ full agonists such as Thiazolidinediones (TZDs) are well established agents for dyslipidemia and type 2 diabetes mellitus (T2D), the side effect profile associated with TZDs has potentiated an imminent need to come up with newer agents that act through this pathway. Several newer derivatives having TZD scaffold have been designed using structure based drug designing technique and computational tools and tested for their PPAR binding affinity and efficacy in combating T2D and some have shown promising activities. This review would focus on the role of PPARs in the management of T2D; recently reported TZD derivatives which acted as agonists of PPAR- γ and its subtypes and are potentially useful in the new drug discovery for the disease.

Keywords: Thiazolidinediones, glitazones, PPAR, antidiabetic drugs, structure activity relationship, drug discovery.

« Previous Next »
[1]
Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 2011; 378(9785): 31-40.
[http://dx.doi.org/10.1016/S0140-6736(11)60679-X] [PMID: 21705069]
[2]
Shin JA, Lee JH, Lim SY, et al. Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness. J Diabetes Investig 2013; 4(4): 334-43.
[http://dx.doi.org/10.1111/jdi.12075] [PMID: 24843675]
[3]
Diabetes Atlas [homepage on internet]. International Diabetes Federation (IDF) [cited 2019 Feb 10]. Available from: http://www.idf.org/diabetesatlas
[4]
Chiarelli F, Di Marzio D. Peroxisome proliferator-activated receptor-γ agonists and diabetes: current evidence and future perspectives. Vasc Health Risk Manag 2008; 4(2): 297-304.
[PMID: 18561505]
[5]
Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004; 27(1): 256-63.
[http://dx.doi.org/10.2337/diacare.27.1.256] [PMID: 14693998]
[6]
Chen KC, Chen CYC. In Silico identification of potent PPAR-γ agonists from traditional chinese medicine: A bioactivity prediction, virtual screening, and molecular dynamics study. Evid Based Complement Alternat Med 2014; 2014192452
[http://dx.doi.org/10.1155/2014/192452] [PMID: 24971147]
[7]
Sargeant RJ, Pâquet MR. Effect of insulin on the rates of synthesis and degradation of GLUT1 and GLUT4 glucose transporters in 3T3-L1 adipocytes. Biochem J 1993; 290(Pt 3): 913-9.
[http://dx.doi.org/10.1042/bj2900913] [PMID: 8457217]
[8]
Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20(5): 649-88.
[PMID: 10529898]
[9]
Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992; 68(5): 879-87.
[http://dx.doi.org/10.1016/0092-8674(92)90031-7] [PMID: 1312391]
[10]
Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res 2006; 45(2): 120-59.
[http://dx.doi.org/10.1016/j.plipres.2005.12.002] [PMID: 16476485]
[11]
Sheu SH, Kaya T, Waxman DJ, Vajda S. Exploring the binding site structure of the PPAR gamma ligand-binding domain by computational solvent mapping. Biochemistry 2005; 44(4): 1193-209.
[http://dx.doi.org/10.1021/bi048032c] [PMID: 15667213]
[12]
Thangavel N, Al Bratty M, Akhtar Javed S, Ahsan W, Alhazmi HA. Targeting peroxisome proliferator-activated receptors using thiazolidinediones: Strategy for design of novel antidiabetic drugs. Int J Med Chem 2017; 20171069718
[http://dx.doi.org/10.1155/2017/1069718] [PMID: 28656106]
[13]
Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002; 53: 409-35.
[http://dx.doi.org/10.1146/annurev.med.53.082901.104018] [PMID: 11818483]
[14]
Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM. Transcriptional regulation of adipogenesis. Genes Dev 2000; 14(11): 1293-307.
[PMID: 10837022]
[15]
Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 1999; 103(11): 1489-98.
[http://dx.doi.org/10.1172/JCI6223] [PMID: 10359558]
[16]
Montagner A, Polizzi A, Fouché E, et al. Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut 2016; 65(7): 1202-14.
[http://dx.doi.org/10.1136/gutjnl-2015-310798] [PMID: 26838599]
[17]
Liu ZM, Hu M, Chan P, Tomlinson B. Early investigational drugs targeting PPAR-α for the treatment of metabolic disease. Expert Opin Investig Drugs 2015; 24(5): 611-21.
[http://dx.doi.org/10.1517/13543784.2015.1006359] [PMID: 25604802]
[18]
Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 1994; 91(15): 7355-9.
[http://dx.doi.org/10.1073/pnas.91.15.7355] [PMID: 8041794]
[19]
Krey G, Braissant O, L’Horset F, et al. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 1997; 11(6): 779-91.
[http://dx.doi.org/10.1210/mend.11.6.0007] [PMID: 9171241]
[20]
Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999; 3(3): 397-403.
[http://dx.doi.org/10.1016/S1097-2765(00)80467-0] [PMID: 10198642]
[21]
Liu S, Hatano B, Zhao M, et al. Role of peroxisome proliferator-activated receptor delta/beta in hepatic metabolic regulation. J Biol Chem 2011; 286(2): 1237-47.
[http://dx.doi.org/10.1074/jbc.M110.138115] [PMID: 21059653]
[22]
Michalik L, Auwerx J, Berger JP, et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 2006; 58(4): 726-41.
[http://dx.doi.org/10.1124/pr.58.4.5] [PMID: 17132851]
[23]
Rosen ED, Spiegelman BM. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 2001; 276(41): 37731-4.
[http://dx.doi.org/10.1074/jbc.R100034200] [PMID: 11459852]
[24]
Juge-Aubry C, Pernin A, Favez T, et al. DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5′-flanking region. J Biol Chem 1997; 272(40): 25252-9.
[http://dx.doi.org/10.1074/jbc.272.40.25252] [PMID: 9312141]
[25]
Hörlein AJ, Näär AM, Heinzel T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995; 377(6548): 397-404.
[http://dx.doi.org/10.1038/377397a0] [PMID: 7566114]
[26]
Zhu Y, Qi C, Calandra C, Rao MS, Reddy JK. Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome proliferator-activated receptor γ. Gene Expr 1996; 6(3): 185-95.
[PMID: 9041124]
[27]
Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol 1998; 10(3): 384-91.
[http://dx.doi.org/10.1016/S0955-0674(98)80015-X] [PMID: 9640540]
[28]
Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2010; 30(5): 894-9.
[http://dx.doi.org/10.1161/ATVBAHA.108.179689] [PMID: 20393155]
[29]
Soccio RE, Chen ER, Lazar MA. Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab 2014; 20(4): 573-91.
[http://dx.doi.org/10.1016/j.cmet.2014.08.005] [PMID: 25242225]
[30]
Cariou B, Charbonnel B, Staels B. Thiazolidinediones and PPARγ agonists: time for a reassessment. Trends Endocrinol Metab 2012; 23(5): 205-15.
[http://dx.doi.org/10.1016/j.tem.2012.03.001] [PMID: 22513163]
[31]
Berger JP, Akiyama TE, Meinke PT. PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci 2005; 26(5): 244-51.
[http://dx.doi.org/10.1016/j.tips.2005.03.003] [PMID: 15860371]
[32]
Wölkart G, Schrammel A, Dörffel K, Haemmerle G, Zechner R, Mayer B. Cardiac dysfunction in adipose triglyceride lipase deficiency: treatment with a PPARα agonist. Br J Pharmacol 2012; 165(2): 380-9.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01490.x] [PMID: 21585347]
[33]
Tsunoda M, Kobayashi N, Ide T, Utsumi M, Nagasawa M, Murakami K. A novel PPARalpha agonist ameliorates insulin resistance in dogs fed a high-fat diet. Am J Physiol Endocrinol Metab 2008; 294(5): E833-40.
[http://dx.doi.org/10.1152/ajpendo.00627.2007] [PMID: 18212024]
[34]
Schäfer HL, Linz W, Falk E, et al. AVE8134, a novel potent PPARα agonist, improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats. Acta Pharmacol Sin 2012; 33(1): 82-90.
[http://dx.doi.org/10.1038/aps.2011.165] [PMID: 22212431]
[35]
Capelli D, Cerchia C, Montanari R, et al. Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode. Sci Rep 2016; 6: 34792.
[http://dx.doi.org/10.1038/srep34792] [PMID: 27708429]
[36]
Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR γ. Cell 1995; 83(5): 803-12.
[http://dx.doi.org/10.1016/0092-8674(95)90193-0] [PMID: 8521497]
[37]
Itoh T, Fairall L, Amin K, et al. Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Mol Biol 2008; 15(9): 924-31.
[http://dx.doi.org/10.1038/nsmb.1474] [PMID: 19172745]
[38]
Shih CY, Chou TC. The antiplatelet activity of magnolol is mediated by PPAR-β/γ. Biochem Pharmacol 2012; 84(6): 793-803.
[http://dx.doi.org/10.1016/j.bcp.2012.06.022] [PMID: 22750553]
[39]
Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr J 2014; 13: 17.
[http://dx.doi.org/10.1186/1475-2891-13-17] [PMID: 24524207]
[40]
García-García HM, Garg S, Brugaletta S, et al. Evaluation of in-stent restenosis in the approach trial (assessment on the prevention of progression by Rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history). Int J Cardiovasc Imaging 2012; 28(3): 455-65.
[http://dx.doi.org/10.1007/s10554-011-9836-z] [PMID: 21359834]
[41]
Balakumar P, Kathuria S. Submaximal PPARγ activation and endothelial dysfunction: new perspectives for the management of cardiovascular disorders. Br J Pharmacol 2012; 166(7): 1981-92.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01938.x] [PMID: 22404217]
[42]
Atamer Y, Atamer A, Can AS, et al. Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus. Braz J Med Biol Res 2013; 46(6): 528-32.
[http://dx.doi.org/10.1590/1414-431X20132818] [PMID: 23802228]
[43]
Lu Y, Ma D, Xu W, Shao S, Yu X. Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis. J Diabetes Investig 2015; 6(1): 78-86.
[http://dx.doi.org/10.1111/jdi.12246] [PMID: 25621136]
[44]
Ahmadian M, Suh JM, Hah N, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med 2013; 19(5): 557-66.
[http://dx.doi.org/10.1038/nm.3159] [PMID: 23652116]
[45]
Bilezikian JP, Josse RG, Eastell R, et al. Rosiglitazone decreases bone mineral density and increases bone turnover in postmenopausal women with type 2 diabetes mellitus. J Clin Endocrinol Metab 2013; 98(4): 1519-28.
[http://dx.doi.org/10.1210/jc.2012-4018] [PMID: 23450056]
[46]
Gerstein HC, Yusuf S, Bosch J, et al. DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368(9541): 1096-105.
[http://dx.doi.org/10.1016/S0140-6736(06)69420-8] [PMID: 16997664]
[47]
Arner P. The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol Metab 2003; 14(3): 137-45.
[http://dx.doi.org/10.1016/S1043-2760(03)00024-9] [PMID: 12670740]
[48]
Kramer D, Shapiro R, Adler A, Bush E, Rondinone CM. Insulin-sensitizing effect of rosiglitazone (BRL-49653) by regulation of glucose transporters in muscle and fat of Zucker rats. Metabolism 2001; 50(11): 1294-300.
[http://dx.doi.org/10.1053/meta.2001.27202] [PMID: 11699047]
[49]
Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7(8): 941-6.
[http://dx.doi.org/10.1038/90984] [PMID: 11479627]
[50]
Jones JR, Barrick C, Kim KA, et al. Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc Natl Acad Sci USA 2005; 102(17): 6207-12.
[http://dx.doi.org/10.1073/pnas.0306743102] [PMID: 15833818]
[51]
Imai T, Takakuwa R, Marchand S, et al. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse. Proc Natl Acad Sci USA 2004; 101(13): 4543-7.
[http://dx.doi.org/10.1073/pnas.0400356101] [PMID: 15070754]
[52]
Rangwala SM, Rhoades B, Shapiro JS, et al. Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity. Dev Cell 2003; 5(4): 657-63.
[http://dx.doi.org/10.1016/S1534-5807(03)00274-0] [PMID: 14536066]
[53]
Kaczanowski S, Zielenkiewicz P. Why similar protein sequences encode similar three M dimensional structures? Theor Chem Acc 2010; 125: 543-50.
[http://dx.doi.org/10.1007/s00214-009-0656-3]
[54]
Russu WA. Thiazolidinedione anti-cancer activity: Is inhibition of microtubule assembly implicated? Med Hypotheses 2007; 68(2): 343-6.
[http://dx.doi.org/10.1016/j.mehy.2006.06.054] [PMID: 16996226]
[55]
Fajeelath F, Baskar L. Thiazolidinediones as a privileged structural scaffold in PPAR agonists: A review. Int J Pharm Chem 2016; 6: 124-41.
[56]
Gale EA. Lessons from the glitazones: a story of drug development. Lancet 2001; 357(9271): 1870-5.
[http://dx.doi.org/10.1016/S0140-6736(00)04960-6] [PMID: 11410214]
[57]
Willson TM, Lambert MH, Kliewer SA. Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu Rev Biochem 2001; 70: 341-67.
[http://dx.doi.org/10.1146/annurev.biochem.70.1.341] [PMID: 11395411]
[58]
Hulin B, Lau CL, Gibbs EM. Synthesis of a biotin conjugate of darglitazone, a new antidiabetic agent. A general protocol for the reversible biotinylation of ketones. Bioorg Med Chem Lett 1993; 3: 703-6.
[http://dx.doi.org/10.1016/S0960-894X(01)81258-0]
[59]
Imran M, Ilyas B. Deepanjali, Khan SA. Recent thiazolididnediones as antidiabetics. J Sci Ind Res (India) 2007; 66: 99-109.
[60]
Alan GEW, Ed. New Horizons in Predictive Toxicology: Current Status and Application 2011.
[61]
Kumar BRP, Soni M, Kumar SS, et al. Synthesis, glucose uptake activity and structure-activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker. Eur J Med Chem 2011; 46(3): 835-44.
[http://dx.doi.org/10.1016/j.ejmech.2010.12.019] [PMID: 21277051]
[62]
Prashantha Kumar BR, Baig NR, Sudhir S, et al. Discovery of novel glitazones incorporated with phenylalanine and tyrosine: synthesis, antidiabetic activity and structure-activity relationships. Bioorg Chem 2012; 45: 12-28.
[http://dx.doi.org/10.1016/j.bioorg.2012.08.002] [PMID: 23064124]
[63]
Gupta D, Ghosh NN, Chandra R. Synthesis and pharmacological evaluation of substituted 5-[4-[2-(6,7-dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolidine-2,4-dione derivatives as potent euglycemic and hypolipidemic agents. Bioorg Med Chem Lett 2005; 15(4): 1019-22.
[http://dx.doi.org/10.1016/j.bmcl.2004.12.041] [PMID: 15686904]
[64]
Tunçbilek M, Bozdağ-Dündar O, Ayhan-Kilcigil G, et al. Synthesis and hypoglycemic activity of some substituted flavonyl thiazolidinedione derivatives--fifth communication: flavonyl benzyl substituted 2,4-thiazolidinediones. Farmaco 2003; 58(1): 79-83.
[http://dx.doi.org/10.1016/S0014-827X(02)01241-7] [PMID: 12595040]
[65]
Kumar BRP, Nanjan MJ, Suresh B, Karvekar MD, Adhikary L. Thiazolidine-2,4-dione and processes thereof. Indian Patent 245830, 2011.
[66]
Kumar BRP, Praveen TK, Nanjan MJ, Karvekar MD. Serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone-induced hyperlipidemia and insulin resistance. Indian J Pharmacol 2007; 39: 299-302.
[http://dx.doi.org/10.4103/0253-7613.39151]
[67]
Kumar BRP, Nanjan MJ. Novel glitazones: design, synthesis, glucose uptake and structure-activity relationships. Bioorg Med Chem Lett 2010; 20(6): 1953-6.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.125] [PMID: 20167487]
[68]
Kumar BRP, Kumar SS, Viral P, et al. Novel glitazones glucose uptake and cytotoxic activities, and structure activity relationships. Med Chem Res 2012; 21: 2689-701.
[http://dx.doi.org/10.1007/s00044-011-9792-0]
[69]
Mehendale-Munj S, Ghosh R, Ramaa CS. Synthesis and evaluation of the hypoglycemic and hypolipidemic activity of novel 5-benzylidene-2,4-thiazolidinedione analogs in a type-2 diabetes model. Med Chem Res 2011; 20: 642-7.
[http://dx.doi.org/10.1007/s00044-010-9359-5]
[70]
Shrivastava SK, Batham A, Sinha SK, Parida TK, Garabadu D, Choubey PK. Design, synthesis and evaluation of novel thiazolidinedione derivatives as anti-hyperglycemic and anti-hyperlipidemic agents. Med Chem Res 2016; 25: 2258-66.
[http://dx.doi.org/10.1007/s00044-016-1675-y]
[71]
Koyama H, Boueres JK, Han W, et al. 5-Aryl thiazolidine-2,4-diones as selective PPARgamma agonists. Bioorg Med Chem Lett 2003; 13(10): 1801-4.
[http://dx.doi.org/10.1016/S0960-894X(03)00257-9] [PMID: 12729668]
[72]
Nomura M, Kinoshita S, Satoh H, et al. (3-substituted benzyl)thiazolidine-2,4-diones as structurally new antihyperglycemic agents. Bioorg Med Chem Lett 1999; 9(4): 533-8.
[http://dx.doi.org/10.1016/S0960-894X(99)00039-6] [PMID: 10098657]
[73]
Yanagisawa H, Fujita T, Fujimoto K, et al. Oxime containing thiazolidinedione derivatives and analogs, their preparation, and their therapeutic use against diabetes and related conditions European Patent 708,098, 1997.
[74]
Georbitz CH, Etter MC. Hydrogen bonds to carboxylate groups. The question of three-center interactions. J Chem Soc Perkin Transactions 1992; 2: 131-5.
[http://dx.doi.org/10.1039/P29920000131]
[75]
Neogi P, Lakner FJ, Medicherla S, et al. Synthesis and structure-activity relationship studies of cinnamic acid-based novel thiazolidinedione antihyperglycemic agents. Bioorg Med Chem 2003; 11(18): 4059-67.
[http://dx.doi.org/10.1016/S0968-0896(03)00393-6] [PMID: 12927868]
[76]
Sahoo SP, Santini C, Boueres JK, Heck JV, Metzger E, Lombardo VK. Preparation of 5-(halo or alkyl)-5-aryl-2,4-thiazolidinedione and oxazolidinedione derivatives as PPAR agonists. PCT Int Appl WO 2000; 0078: 312.
[77]
Darwish KM, Salama I, Mostafa S, Gomaa MS, Helal MA. Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists. Eur J Med Chem 2016; 109: 157-72.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.049] [PMID: 26774923]
[78]
Yasmin S, Capone F, Laghezza A, et al. Novel benzylidene thiazolidinedione derivatives as partial PPARγ agonists and their antidiabetic effects on type 2 diabetes. Sci Rep 2017; 7(1): 14453.
[http://dx.doi.org/10.1038/s41598-017-14776-0] [PMID: 29089569]
[79]
Mohammed Iqbal AK, Khan AY, Kalashetti MB, Belavagi NS, Gong YD, Khazi IAM. Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring. Eur J Med Chem 2012; 53: 308-15.
[http://dx.doi.org/10.1016/j.ejmech.2012.04.015] [PMID: 22575535]
[80]
Ahmadi A, Khalili M, Samavat S, Shahbazi E, Nahri-Niknafs B. Synthesis and evaluation of the hypoglycemic and hypolipidemic activity of novel arylidene thiazolidinedione analogson a type 2 diabetes model. Pharm Chem J 2016; 50: 165-71.
[http://dx.doi.org/10.1007/s11094-016-1416-z]
[81]
Nazreen S, Alam MS, Hamid H, et al. Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-c agonists. Eur J Med Chem 2014; 87: 175-85.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.010] [PMID: 25255433]
[82]
Fujimori S, Murakami K, Tsunoda M. Preparation of substituted benzylthiazolidine-2,4-dione derivatives as ligands of human peroxisome proliferator-activated receptor. PCT Int Appl WO 2001; 0114: 350.
[83]
Madhavan GR, Chakrabarti R, Vikramadithyan RK, et al. Synthesis and biological activity of novel pyrimidinone containing thiazolidinedione derivatives. Bioorg Med Chem 2002; 10(8): 2671-80.
[http://dx.doi.org/10.1016/S0968-0896(02)00107-4] [PMID: 12057656]
[84]
Lohray BB, Bhushan V, Reddy AS, et al. Novel euglycemic and hypolipidemic agents. 4. Pyridyl- and quinolinyl-containing thiazolidinediones. J Med Chem 1999; 42(14): 2569-81.
[http://dx.doi.org/10.1021/jm980622j] [PMID: 10411477]
[85]
Agrawal R, Jain P, Dikshit SN. Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma (γ) agonist. Mini Rev Med Chem 2012; 12(2): 87-97.
[http://dx.doi.org/10.2174/138955712798995048] [PMID: 22372600]
[86]
Pfahl M, Tachdijan C, Al-Shamma HA, Fanju A, Pleynet DPN, Spran LW. Preparation of benzylidene thiazolidinediones and analoga as antidiabetics. PCT Int Appl WO 2001; 0016: 122.
[87]
Lohray BB, Bhushan V. Indole containing thiazolidine-2,4-diones as novel euglycemic and hypolipidemic agents: DRF-2189. Drugs Future 1999; 24: 751-7.
[http://dx.doi.org/10.1358/dof.1999.024.07.548424]
[88]
Oguchi M, Wada K, Honma H, et al. Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones. J Med Chem 2000; 43(16): 3052-66.
[http://dx.doi.org/10.1021/jm990522t] [PMID: 10956213]
[89]
Madhavan GR, Chakrabarti R, Kumar SKB, et al. Novel phthalazinone and benzoxazinone containing thiazolidinediones as antidiabetic and hypolipidemic agents. Eur J Med Chem 2001; 36(7-8): 627-37.
[http://dx.doi.org/10.1016/S0223-5234(01)01257-0] [PMID: 11600232]
[90]
Lohray VB, Lohray BB, Paraselli RB, Rajagopalan R, Chakrabarti R. Preparation of substituted thiazolidinediones having antidiabetic, hypolipidemic and antihypertensive properties United States Patent 6,313,113, 2001.
[91]
Jeon R, Park S. Synthesis and biological activity of benzoxazole containing thiazolidinedione derivatives. Arch Pharm Res 2004; 27(11): 1099-105.
[http://dx.doi.org/10.1007/BF02975111] [PMID: 15595409]
[92]
Shriram SP, Veerapur VP. Benzisoxazle containing thiazolidinediones as peroxisome proliferator activated receptor-γ agonists: Design, molecular docking, synthesis and antidiabetic studies. Sch Acad J Pharm 2014; 3: 26-37.
[93]
Sattigeri JA, Salman M. Preparation of phenyl acetylene derivatives as agonists of PPAR receptors PCT Int Appl WO 058813, 2005.
[94]
Nazreen S, Alam MS, Hamid H, et al. Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression. Bioorg Med Chem Lett 2014; 24(14): 3034-42.
[http://dx.doi.org/10.1016/j.bmcl.2014.05.034] [PMID: 24890090]
[95]
Onota M, Iwai Y. Preparation of benzoic acids and thiazolidinediones for N-benzyldioxothiazolidinyl-benzamides as antidiabetic agents Japanese Patent 354,664, 2001.
[96]
Shashikant RP, Prajact K, Ashwini P, Ana N, Kittur BS. Studies on the synthesis of novel thiazolidinedione derivatives with antidiabetic activity. Iran J Pharm Sci 2009; 5: 225-30.
[97]
Maji D, Samanta S. Novel thiazolidinedione-5-acetic-acid-peptide hybrid derivatives as potent antidiabetic and cardioprotective agents. Biomed Pharmacother 2017; 88: 1163-72.
[http://dx.doi.org/10.1016/j.biopha.2017.01.160]
[98]
Cho H, Wu Y, Choi CH. inventor; Thiazolidinedione derivative and use there of United States Patent US 8637558, 2014.
[99]
Kositprapa U, Nangia A, Cardinal J, Goldfarb RI. inventor; Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative United States Patent US 8309125, 2012.
[100]
Colca GR, Kletzien RF. inventor; PPAR-sparing thiazolidinediones for the treatment of kidney related diseases. Worldwide Patent WO 2012149083, 2012 Nov.
[101]
Colca GR, Gadwood RC, Parker T. inventor; Thiazolidinedione analogues Worldwide Patent WO 2011133611, 2011 Oct.
[102]
Kositprapa U, Goldfarb RI, Cardinal JR, Nangia A. inventor; Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative United States Patent US 7959946, 2011 June.
[103]
Colca GR, Larsen SD, Tanis SP, Parker T, Gadwood R. inventor; Thiazolidinedione analogues Worldwide Patent WO 2010105048, 2010 Sept.
[104]
Colca GR, Gadwood RC, Parker T. inventor; Thiazolidinedione analogues for the treatment of hypertension Worldwide Patent WO 2009038681, 2009 Mar.
[105]
Gaul M, Kim A, Searle LL, et al. inventor; Substituted phenoxy thiazolidinediones as estrogen related receptor-alpha modulators. Worldwide patent WO 2008109727, 2008 Sept.
[106]
Blackler PDJ, Giles RG, Moore S, Sasse MJ. inventor; Thiazolidinedione derivative and its use as antidiabetic United States Patent US 7358366, 2008 Apr.
[107]
Colca GR, Kletzien RF. inventor; Thiazolidinedione analogues for the treatment of hypertension and for lowering lipids United States Patent US WO 2007109037, 2007 Sept.
[108]
Buxton PC, Mackenzie DC. inventor; Substituted thiazolidinedione derivatives. United States Patent US RE39384, 2006 Nov.
[109]
Giles RG, Lewis NJ, Quick JK. inventor; Process for the preparation of thiazolidinedione derivatives. United States Patent US 7091359, 2006 Aug.
[110]
Pospisilik K, Zhu J, Picha F. inventors; Processes for making thiazolidinedione derivatives and compounds thereof Worldwide Patent WO 2004101560, 2004 Nov.
[111]
Szilvassy Z, Literati NP. inventors; Use of a thiazolidinedione for the reduction of side effects of chemotherapy. Worldwide Patent WO 2004045611, 2004 June.
[112]
Lala RG, Gadkari PN, Shah MJ, Shah JR. inventors; Improved process for preparation of thiazolidinedione derivatives Worldwide Patent WO 2004024059, 2004 Mar.
[113]
Antarkar AK, Lala RG, Kamdar NM, Gadkari PN, Shah MJ, Shah JR. inventors; Multilayer tablets containing thiazolidinedione and biguanides and method for producing them Worldwide Patent WO 2003105809, 2003 Dec.
[114]
Craig AS, Ho TCT. inventors; Toluenesulfonate salts of a thiazolidinedione derivative Worldwide Patent WO 2003050111, 2003 June.
[115]
Giles R, Lewis N, Quick J. inventors; Process for the preparation of thiazolidinedione derivatives United States Patent US 20020120150, 2002 Aug.
[116]
Lewis K, Lilliott NJ, Mackenzie DC. inventors; Novel composition based on a thiazolidinedione and metformin and use. Worldwide Patent WO 2001035941, 2002 Aug.
[117]
Vyas S. inventor; Process for the preparation of pyridine derivative. United States Patent US 20020115866, 2002 Aug.
[118]
Smithkline BP, Lilliott NJ, Mackenzie DC. inventors; Novel composition based on a thiazolidinedione and metformin and use. Worldwide Patent WO 2001035941, 2002 May.
[119]
Ohnota M, Orita K. inventors; Novel stable crystal of thiazolidinedione derivative and process for producing the same. Worldwide Patent WO 2001081327, 2001 Nov.
[120]
Scalone M. inventor; Processes for the preparation of thiazolidinedione derivatives and intermediates. Worldwide Patent WO 2001079202, 2001 Oct.
[121]
Yakubu-Madus FE, Stramm LE, Johnson WT, Vignati L. inventors; Synergetic use of thiazolidinediones with glucagon-like peptide- 1 and agonists thereof to treat non-insulin dependent diabetes Worldwide Patent WO 2000078333, 2001 July.
[122]
Meguro K, Fujita T, Hatanaka C, Ooi S. inventors; Pyridine and thiazolidinedione derivatives United States Patent US RE36575, 2000 Feb.
[123]
Buckingham RE, Smith SA. inventors; Use of thiazolidinediones for the treatment of hyperglycaemia Worldwide Patent WO 1999018944, 1999 Apr.
[124]
Buckingham RE, Smith SA. inventors; Treatment of diabetes with thiazolidinedione, insulin secretagogue and alpha glucocidase inhibitor Worldwide Patent WO 1999003478, 1999.
[125]
Dixit VA, Bharatam PV. SAR and computer aided drug design approaches in the discovery of peroxisome proliferator activated receptor γ activators: A perspective. J Comput Med 2013; 2013406049
[http://dx.doi.org/10.1155/2013/406049]
[126]
Mudur G. Researchers question ethics of diabetes drug trial. BMJ 2002; 325(7360): 353.
[http://dx.doi.org/10.1136/bmj.325.7360.353/a] [PMID: 12183295]
[127]
Balaglitazone [homepage on internet]. [cited 2019 Feb 10] Available from: https://www.pharmacodia.com/yaodu/html/v1/chemicals/5339541e2e03e582f15eadb54b92a80d.html
[128]
Araki K, Yachi M, Hagisawa Y, et al. Antidiabetic characterization of CS-011: a new thiazolidinedione with potent insulin-sensitizing activity. Diabetes 2000; 49: A105.
[129]
Uchiyama M, Iwabuchi H, Tsuruta F, et al. Pharmacokinetics, metabolism, and disposition of rivoglitazone, a novel peroxisome proliferator-activated receptor γ agonist, in rats and monkeys. Drug Metab Dispos 2011; 39(4): 653-66.
[http://dx.doi.org/10.1124/dmd.110.036194] [PMID: 21177486]
[130]
Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 2001; 134(1): 61-71.
[http://dx.doi.org/10.7326/0003-4819-134-1-200101020-00014] [PMID: 11187421]
[131]
Haber EP, Ximenes HM, Procópio J, Carvalho CR, Curi R, Carpinelli AR. Pleiotropic effects of fatty acids on pancreatic beta-cells. J Cell Physiol 2003; 194(1): 1-12.
[http://dx.doi.org/10.1002/jcp.10187] [PMID: 12447984]
[132]
Briscoe CP, Tadayyon M, Andrews JL, et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem 2003; 278(13): 11303-11.
[http://dx.doi.org/10.1074/jbc.M211495200] [PMID: 12496284]
[133]
Lefkowitz RJ. Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol Sci 2004; 25(8): 413-22.
[http://dx.doi.org/10.1016/j.tips.2004.06.006] [PMID: 15276710]
[134]
Kotarsky K, Nilsson NE, Flodgren E, Owman C, Olde B. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem Biophys Res Commun 2003; 301(2): 406-10.
[http://dx.doi.org/10.1016/S0006-291X(02)03064-4] [PMID: 12565875]
[135]
Salehi A, Flodgren E, Nilsson NE, et al. Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion. Cell Tissue Res 2005; 322(2): 207-15.
[http://dx.doi.org/10.1007/s00441-005-0017-z] [PMID: 16044321]

Rights & Permissions Print Cite
Article Metrics
34
3
© 2024 Bentham Science Publishers | Privacy Policy