145370-34-9

Upstream product

• 145370-30-5 3-fluoro-benzoic acid 2-acetyl-phenyl ester 
• 1711-07-5 3-fluorobenzoyl chloride 
• 118-93-4 o-hydroxyacetophenone 

Downstream Products

• 1744-33-8 3'-Fluoroflavone 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of 2-Phenyl-4H-chromen-4-one derivatives as polyfunctional compounds against Alzheimer’s disease

Polyfunctional compounds comprise a novel class of therapeutic agents for the treatment of multi-factorial diseases. A series of 2-Phenyl-4H-chromen-4-one and its derivatives (5a–n) were designed, synthesized, and evaluated for their poly-functionality against acetylcholinestrase (AChE) and advanced glycation end products (AGEs) formation inhibitors against Alzheimer’s disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit AChE AGEs formation with additional radical scavenging activity. Especially, 5m, 5b, and 5j displayed the greatest ability to inhibit AChE (IC50 = 8.0, 8.2, and 11.8 nM, respectively) and AGEs formation (IC50 = 55, 79, and 54 μM, respectively) with good antioxidant activity. Molecular docking studies explored the detailed interaction pattern with active, peripheral, and mid-gorge sites of AChE. These compounds, exhibiting such multiple pharmacological activities, can be further taken a lead for the development of potent drugs for the treatment of Alzheimer’s disease.

Pharmacophore and docking-based hierarchical virtual screening for the designing of aldose reductase inhibitors: Synthesis and biological evaluation

A set of 54 studied flavonoid inhibitors of aldose reductase (ALR2) enzyme has been utilized for pharmacophore modeling and 3D-QSAR analysis using "PHASE" program of Schr?dinger software. The generated pharmacophore model (AADRR.1109) was challenged to screen "PHASE" database to identify new ALR2 inhibitors. The retrieved hits were employed for docking analysis and pharmacokinetic parameter calculation to obtain orally active molecules. To predict the activity of final retrieved hits, 3D-QSAR model was developed, and the best model was selected on the basis of various statistical parameters (Rtrain 2 0.719; Q test 2 0.647 and SD 0.663). Totally five screened molecules which showed better enhanced predicted activity were synthesized and evaluated for in vitro ALR2 inhibitory activity. All tested molecules showed ALR2 inhibitory activity (IC50) below 40 μM. Additionally, the free radical scavenging potential of synthesized molecules was also determined which played a useful role to control the progression of diabetic complications. All molecules showed good antioxidant potential, thus the designed molecules, in future, could be explored to ameliorate the development of diabetic complications.

Benzoflavone activators of the cystic fibrosis transmembrane conductance regulator: Towards a pharmacophore model for the nucleotide-binding domain

Our previous screen of flavones and related heterocycles for the ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel indicated that UCCF-029, a 7,8-benzoflavone, was a potent activator. In the present study, we describe the synthesis and evaluation, using cell-based assays, of a series of benzoflavone analogues to examine structure-activity relationships and to identify compounds having greater potency for activation of both wild type CFTR and a mutant CFTR (G551D-CFTR) that causes cystic fibrosis in some human subjects. Using UCCF-029 as a structural guide, a panel of 77 flavonoid analogues was prepared. Analysis of the panel in FRT cells indicated that benzannulation of the flavone A-ring at the 7,8-position greatly improved compound activity and potency for several flavonoids. Incorporation of a B-ring pyridyl nitrogen either at the 3- or 4-position also elevated CFTR activity, but the influence of this structural modification was not as uniform as the influence of benzannulation. The most potent new analogue, UCCF-339, activated wild-type CFTR with a Kd of 1.7 μM, which is more active than the previous most potent flavonoid activator of CFTR, apigenin. Several compounds in the benzoflavone panel also activated G551D-CFTR, but none were as active as apigenin. Pharmacophore modeling suggests a common binding mode for the flavones and other known CFTR activators at one of the nucleotide-binding sites, allowing for the rational development of more potent flavone analogues.