Development of a new class of benzoylpyrrole-based PPARα/γ activators.
Starting with a subtle blood glucose-lowering effect of a TGF-β inhibitor, we designed and synthesized a series of benzoylpyrrole-based carboxylic acids as PPARs activators. Among these compounds, 10sNa exhibited favorable blood glucose-lowering effect without body weight gain. We assume that the beneficial effect of 10sNa is attributed to not only its compound PPARα agonistic activity but also its PPARγ partial agonistic activity.
Dainippon Sumitomo Pharma Co, Ltd, Drug Research Division, Chemistry Research Laboratories, Osaka, Japan.
Kantaro
K
Ushiroda
Katsunori
K
Maruta
Makoto
M
Kitoh
Kiyotaka
K
Iwai
Jun
J
Nagamine
Atsushi
A
Tsuchida
Mutsuo
M
Taiji
Ryu
R
Nagata
D000085:Acetates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship
D000085:Acetates; D002264:Carboxylic Acids; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D011758:Pyrroles