Development of a new class of benzoylpyrrole-based PPARα/γ activators

Kantaro Ushiroda; Katsunori Maruta; Makoto Kitoh; Kiyotaka Iwai; Jun Nagamine; Atsushi Tsuchida; Mutsuo Taiji; Ryu Nagata

doi:10.1016/j.bmcl.2010.11.032

Development of a new class of benzoylpyrrole-based PPARα/γ activators

Bioorg Med Chem Lett. 2011 Jan 1;21(1):220-4. doi: 10.1016/j.bmcl.2010.11.032. Epub 2010 Nov 12.

Authors

Kantaro Ushiroda¹, Katsunori Maruta, Makoto Kitoh, Kiyotaka Iwai, Jun Nagamine, Atsushi Tsuchida, Mutsuo Taiji, Ryu Nagata

Affiliation

¹ Dainippon Sumitomo Pharma Co, Ltd, Drug Research Division, Chemistry Research Laboratories, Osaka, Japan.

PMID: 21130649
DOI: 10.1016/j.bmcl.2010.11.032

Abstract

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.

MeSH terms

Acetates / chemistry*
Acetates / pharmacokinetics
Acetates / therapeutic use
Animals
Carboxylic Acids / chemistry*
Carboxylic Acids / pharmacokinetics
Carboxylic Acids / therapeutic use
Hyperglycemia / drug therapy
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacokinetics
Hypoglycemic Agents / therapeutic use
Male
Mice
Mice, Obese
Obesity / drug therapy
PPAR alpha / agonists*
PPAR alpha / metabolism
PPAR gamma / agonists*
PPAR gamma / metabolism
Pyrroles / chemistry*
Pyrroles / pharmacokinetics
Pyrroles / therapeutic use
Rats
Structure-Activity Relationship

Substances

Acetates
Carboxylic Acids
Hypoglycemic Agents
PPAR alpha
PPAR gamma
Pyrroles