4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARalpha/gamma agonists. Part. II: Synthesis and pharmacological evaluation of oxime and acidic head group structural variations

Bioorg Med Chem Lett. 2009 May 15;19(10):2683-7. doi: 10.1016/j.bmcl.2009.03.143. Epub 2009 Apr 1.

Abstract

Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a deficiency in pancreatic beta-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARalpha, PPARgamma and PPARbeta/(delta). In this study, we were interested in designing novel PPARgamma selective agonists and/or dual PPARalpha/gamma agonists. Based on the typical topology of synthetic PPAR agonists, we focused our design approach on using 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as a novel cyclic scaffold with oxime and acidic head group structural variations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus, Type 2 / drug therapy
  • Disease Models, Animal
  • Humans
  • Mice
  • Oximes / chemistry*
  • PPAR alpha / agonists*
  • PPAR alpha / metabolism
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • 4,4-dimethyl-1,2,3,4-tetrahydroquinoline
  • Oximes
  • PPAR alpha
  • PPAR gamma
  • Quinolines