Indenone Derivatives:  A Novel Template for Peroxisome Proliferator-Activated Receptor γ (PPARγ) Agonists

Abstract

Agonists of peroxisome proliferator-activated receptor γ (PPAR γ) are of interest as a treatment for diabetes, which prompted the identification of a new class of non-TZD PPAR γ agonist. Moreover, compound 14c has displayed the most active agonistic activity with an EC50 value of 50 nM, in addition to exhibiting a new binding mode in the X-ray cocrystal structure.

Selective inhibition of activated stellate cells and protection from carbon tetrachloride-induced liver injury in rats by a new PPARγ agonist KR62776

“…In addition, Bae et al (2003) demonstrated that TRO induced apoptosis in human hepatoma cell lines via a PPARγ-independent pathway by activating the cell-death related stress-activated protein kinases. Previous studies showed that KR62776 binds to the ligand binding domain of PPARγ in a different mode from that of rosiglitazone, which is a well known PPARγ ligand with a thiazolidinedione structure (Ahn et al, 2006). Since KR62776 showed no or little effect on human hepatoma cells, it is believed that the novel structure of KR62776 might be important for exhibiting the selective inhibitory action on stellate cells without affecting the cells with a hepatic origin.…”

Visible‐light‐catalyzed Tandem Difluoroacetylation–Intramolecular Cyclization of 1,3‐Diarylpropynones: Access to Difluoroacetylated Indenones

“…The indenone scaffold is considered ap rivileged scaffold due to its presence in aw ide range of biologically active natural (pauciflorol F, [17] and euplectin [18] )a nd synthetic molecules including estrogen binding receptors [19] and antimicrobial, [20] antidiabetic [21] and anticancer [22] molecules. Additionally,s everal indenone derivatives have been developed as drug molecules (donepezil as anti-Alzheimer's disease [23] and indacrinone as antihypertensive [24] drugs) or are potential future drugs (indotecan and indimitecan as anticancer, [25] indotecan and AM13-55 as antileishmanial [26] drugs).…”

A facile trifluoromethylthiolation of 3-chloro-1H-inden-1-ones employing AgSCF3 and KI

“…Indenone-containing compounds were widely employed as agonists for estrogen receptor 23 and peroxisome proliferator-activated receptor γ (PPARγ). 24 They also has been used as cyclooxygenase-2 (COX-2) 25 and topoisomerase I (Top I) 26 inhibitors and so on . 27 Therefore, incorporation of the SCF3 group into the indenone moiety can lead to novel series of heterocyclic scaffolds and will bring about further advances in the pharmacological applications.…”