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.
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.
UMR GICC, Laboratoire de Chimie Organique, UFR des Sciences Pharmaceutiques, Tours, France.
Cécile
C
Parmenon
Jérôme
J
Guillard
Daniel-Henri
DH
Caignard
Nathalie
N
Hennuyer
Bart
B
Staels
Valérie
V
Audinot-Bouchez
Jean-Albert
JA
Boutin
Catherine
C
Dacquet
Alain
A
Ktorza
Marie-Claude
MC
Viaud-Massuard
D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D010091:Oximes / Q000737:chemistry*; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
C528892:4,4-dimethyl-1,2,3,4-tetrahydroquinoline; D010091:Oximes; D047493:PPAR alpha; D047495:PPAR gamma; D011804:Quinolines