1124174-55-5

Upstream product

• 111841-07-7 2-hydroxy-4-(tetrahydropyran-2-yloxy)acetophenone 
• 68-12-2 N,N-dimethyl-formamide 
• 89-84-9 2',4'-dihydroxy-4-acetophenone 
• 110-87-2 3,4-dihydro-2H-pyran 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 

Downstream Products

• 1013634-99-5 7-hydroxy-3-iodo-4H-chromen-4-one 
• 1616248-08-8 7-((2-chlorobenzyl)oxy)-3-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one 
• 1616248-09-9 7-((3-bromobenzyl)oxy)-3-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one 
• 1616248-10-2 7-((2-bromobenzyl)oxy)-3-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one 
• 1616248-11-3 7-((4-(trifluoromethyl)benzyl)oxy)-3-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one 
• 1616248-12-4 7-((3-(trifluoromethyl)benzyl)oxy)-3-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one 
• 1422513-56-1 3-(3-methoxyphenyl)-8,8-dimethyl-4-oxo-4H,8H-benzo[1,2-b:3,4-b']dipyran 
• 63286-38-4 3-(3,4-dimethoxyphenyl)-8,8-dimethyl-4-oxo-4H,8H-benzo[1,2-b:3,4-b']dipyran 
• 31273-64-0 3-(4-methoxyphenyl)-8,8-dimethyl-4-oxo-4H,8H-benzo[1,2-b:3,4-b']dipyran 
• 1422513-59-4 3-(2,4-dimethoxyphenyl)-8,8-dimethylpyrano[2,3-f]chromen-4(8H)-one 
• 62502-14-1 3-(3,4-methylenedioxyphenyl)-8,8-dimethyl-4-oxo-4H,8H-benzo[1,2-b:3,4-b']dipyran 
• 1422513-60-7 8,8-dimethyl-3-(2,3,4-trimethoxyphenyl)pyrano[2,3-f]chromen-4(8H)-one 
• 1422513-62-9 3-(2-fluoro-3-methoxyphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one 
• 1422513-63-0 3-(4-acetylphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one 

Relevant academic research and scientific papers

Highly selective carbamate-based butyrylcholinesterase inhibitors derived from a naturally occurring pyranoisoflavone

This current study described the design and synthesis of a series of derivatives based on a natural pyranoisaflavone, which was obtained from the seeds of Millettia pachycarpa and displayed attractive BChE inhibition and high selectivity in our previous study. The inhibitory potential of all derivatives against two cholinesterases was evaluated. Only a few compounds demonstrated AChE inhibitory activity at the tested concentrations, while 26 compounds showed significant inhibition on BChE (the IC50 values varied from 9.34 μM to 0.093 μM), most of them presented promising selectivity to ward BChE. Prediction of ADME properties for 7 most active compounds was performed. Among them, 9g (IC50 = 222 nM) and 9h (IC50 = 93 nM) were found to be the most potent BChE inhibitors with excellent selectivity over AChE (SI ratio = 1339 and 836, respectively). The kinetic analysis demonstrated both of them acted as mixed-type BChE inhibitors, while the molecular docking results indicated that they interacted with both residues in the catalytic active site. A cytotoxicity test on PC12 cells showed that both 9g and 9h had a therapeutic safety range similar to tacrine. Overall, the results indicate that 9h could be a good candidate of BChE inhibitors.

Screening, synthesis, and evaluation of novel isoflavone derivatives as inhibitors of human Golgi β-galactosidase

The genes GLB1 and GALC encode GLB1 isoform 1 and galactocerebrosidase, respectively, which exhibit β-galactosidase activity in human lysosomes. GLB1 isoform 1 has been reported to play roles in rare lysosomal storage diseases. Further, its β-galactosidase activity is the most widely used biomarker of senescent and aging cells; hence, it is called senescence-associated β-galactosidase. Galactocerebrosidase plays roles in Krabbe disease. We previously reported a novel β-galactosidase activity in the Golgi apparatus of human cells; however, the protein responsible for this activity could not be identified. Inhibitor-derived chemical probes can serve as powerful tools to identify the responsible protein. In this study, we first constructed a cell-based high-throughput screening (HTS) system for Golgi β-galactosidase inhibitors, and then screened inhibitors from two compound libraries using the HTS system, in vitro assay, and cytotoxicity assay. An isoflavone derivative was identified among the final Golgi β-galactosidase inhibitor compound hits. Molecular docking simulations were performed to redesign the isoflavone derivative into a more potent inhibitor, and six designed derivatives were then synthesized. One of the derivatives, ARM07, exhibited potent inhibitory activity against β-galactosidase, with an IC50 value of 14.8 μM and competitive inhibition with Ki value of 13.3 μM. Furthermore, the in vitro and cellular inhibitory activities of ARM07 exceeded those of deoxygalactonojirimycin. ARM07 may contribute to the development of affinity-based chemical probes to identify the protein responsible for the newly discovered Golgi β-galactosidase activity. The therapeutic relevance of ARM07 against lysosomal storage diseases and its effect on senescent cells should be evaluated further.

Isoflavone type compound as well as preparation method and application thereof

The invention provides an isoflavone type compound and a preparation method thereof. A structural formula of the isoflavone type compound is shown as a formula and the formula is shown in the description, wherein R is a formula shown in the description, a

Synthesis, structure-activity relationships and biological evaluation of barbigerone analogues as anti-proliferative and anti-angiogenesis agents

A series of barbigerone analogues (7a-7w, 13a-13x) were designed, synthesized and biologically evaluated for their anti-proliferative and anti-angiogenic activities. Among these compounds, compound 13a exhibited the most potent inhibitory effect on the proliferation of HUVECs, HepG2, A375, U251, B16, and HCT116 cells (IC50 = 3.80, 0.28, 1.58, 3.50, 1.09 and 0.68 μM, respectively). Compound 13a inhibited the angiogenesis in zebrafish embryo assay in a concentration-dependent manner. Furthermore, 13a also effectively inhibited the migration and capillary like tube formation of human umbilical vein endothelial cell in vitro. These results support the further investigation of this class of compounds as potential anti-proliferative and anti-angiogenesis agents.

7-Hydroxy-benzopyran-4-one derivatives: A novel pharmacophore of peroxisome proliferator-activated receptor α and -γ (PPARα and γ) dual agonists

Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARα and γ agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead PPAR ligands were identified from "natraceuticals" and synthetic analogues. In total, 77 molecules, including chalcones, flavones, flavanones, isoflavones, and pyrazole derivatives, were screened and structure-activity relationship studies of the dual agonists undertaken. Compounds 68, 70, 72, and 76 were identified as novel and potent dual PPARα and γ agonists. These novel molecules may have the potential to be the future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome. 2009 American Chemical Society.

FLAVONOID PPAR AGONISTS

The present invention relates to PPAR agonists, and their use in therapy including the treatment of disease. In particular, the invention relates to flavonoid compounds which are PPAR-gamma agonists and/or PPAR alpha/gamma dual agonists.