%0 Journal Article
%T Synthesis of N-(6-(4-(Piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide Derivatives for the Treatment of Metabolic Syndrome
%A Nabajyoti Deka
%A Swapnil Bajare
%A Jessy Anthony
%A Amrutha Nair
%A Anagha Damre
%A Dharmeshkumar Patel
%A Chandrika B-Rao
%A H. Sivaramakrishnan
%A Shivaprakash Jagalur Mutt
%A Chandan Wilankar
%A Rosalind Marita
%J International Journal of Medicinal Chemistry
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/201580
%X Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs) are potent PPAR¦Ã ligand and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. Here we report synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives as an alternate remedy for insulin resistance. 1. Introduction Metabolic disorder is a highly widespread clinical entity. Although obesity and insulin resistance are not synonymous with the metabolic syndrome, they are integral features in this derangement of adipocyte physiology and carbohydrate metabolism. PPARs play a key role in adipocyte differentiation and insulin sensitivity [1]. They are lipid sensors known to govern numerous biological processes. There are three PPAR subtypes (¦Á, ¦Â, and ¦Ã) and they regulate the expression of numerous genes involved in a variety of metabolic pathways [2]. Roles of PPAR¦Á and PPAR¦Ã are now quite well known, particularly since their pharmacologic ligands have been marketed. PPAR¦Á and PPAR¦Ã are the target of the lipid-normalizing class of fibrates (e.g., fenofibrate and gemfibrozil) and the antidiabetic class of thiazolidinediones (e.g., rosiglitazone and pioglitazone), respectively [3]. PPAR¦Ã is expressed most abundantly in adipose tissue and is a master regulator of adipogenesis [4, 5]. Thiazolidinediones (Figure 1), selective activators of PPAR¦Ã, have been marketed as antidiabetic drugs. They enhance insulin action, improve glycemic control, reduce the level of glycohemoglobin (HbA1C), and have variable effects on serum triglyceride levels in type 2 diabetic patients. Despite their efficacy, they possess a number of side effects [6, 7], including weight gain and peripheral edema, increased risks of congestive heart failure, and increased rate of bone fracture. The weight gain is likely due to multiple interacting factors, including increased adiposity and fluid retention. Moreover, the assumption that TZD treatment causes a significant increase in the risk of myocardial infarction and an increase in the risk of death from cardiovascular events in patients with type 2 diabetes. More importantly, TZDs treatment was recently shown to decrease bone formation and accelerated bone loss in
%U http://www.hindawi.com/journals/ijmc/2013/201580/