916482-40-1

Upstream product

• 916482-31-0 ethyl 2-[(4,6-dichloropyrimidin-2-yl)sulfanyl]-2-(naphthalene-1-yl)acetate 
• 87-59-2 2,3-Dimethylaniline 

Downstream Products

• 916482-19-4 C₂₄H₂₀ClN₃O₂S 

Relevant academic research and scientific papers

Rational design of a pirinixic acid derivative that acts as subtype-selective PPARγ modulator

Peroxisome proliferator-activated receptor γ (PPARγ) is involved in glucose and lipid homeostasis. PPARγ agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPARγ modulators (SPPARγMs) was developed, which are believed to show less side effects than full PPARγ agonists. We have previously shown that α-substitution of pirinixic acid, a moderate agonist of PPARα and PPARγ, leads to low micromolar active balanced dual agonists of PPARα and PPARγ. Herein we present modifications of pirinixic acid leading to subtype-selective PPARγ agonists and furthermore the development of a selective PPARγ modulator guided by molecular docking studies.

α-alkyl substituted pirinixic acid derivatives as potent dual agonists of the peroxisome proliferator activated receptor alpha and gamma

Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors, playing a pivotal role in energy homeostasis. Activators of the PPARα subtype are in widespread use for the treatment of hyperlipidemia, while activators of the PPARγ subtype are in clinical use for the treatment of type-2 diabetes. Since both of these diseases are frequently associated, the combined treatment with one drug simultaneously activating PPARα and PPARγ seems worthwhile. Starting with pirinixic acid, which is a moderately active dual PPARα/γ agonist, we improved potency at the human PPARα and PPARγ by substituting the a-position with an aliphatic chain. The maximal effect was achieved at a chain length of four and six carbons, respectively, leading to an activity induction by a factor of 36 for PPARα and 18 for PPARγ, respectively.