title: Synthesis of N-(5-chloro-6-(quinolin-3-yloxy)pyridin-3-yl)benzenesulfonamide derivatives as non-TZD peroxisome proliferator-activated receptor γ (PPARγ) agonist.
abstract: The thiazolidinediones (TZDs) are a class of oral antidiabetic drugs that improve insulin sensitivity in patients with type 2 diabetes. Although the mechanism by which the TZDs lower insulin resistance is unclear, they are known to target the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor. Ligands for PPARγ regulate adipocyte production and secretion of fatty acids as well as glucose metabolism, resulting in increased insulin sensitivity in adipose tissue, liver, and skeletal muscle. However, TZDs have several adverse effects, including weight gain and liver toxicity. Herein we report identification of non-TZD PPARγ agonists which exhibit beneficial effects similar to that of TZDs in animal models, but without the associated adverse effects.
authors.affiliation: Department of Medicinal Chemistry, Piramal Healthcare Limited, Goregaon (E), Mumbai 400 063, Maharashtra, India.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Bajare
authors.forename: Jessy
authors.initials: J
authors.lastname: Anthony
authors.forename: Amrutha
authors.initials: A
authors.lastname: Nair
authors.forename: Rosalind
authors.initials: R
authors.lastname: Marita
authors.forename: Anagha
authors.initials: A
authors.lastname: Damre
authors.forename: Dharmeshkumar
authors.initials: D
authors.lastname: Patel
authors.forename: Chandrika
authors.initials: C
authors.lastname: Rao
authors.forename: H
authors.initials: H
authors.lastname: Sivaramakrishnan
authors.forename: Nabajyoti
authors.initials: N
authors.lastname: Deka
mesh_terms: D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D011804:Quinolines; D013449:Sulfonamides