184774-53-6

Upstream product

• 52119-37-6 3-<4-(Dimethylamino)phenyl>-1-(4-methoxyphenyl)prop-2-en-1-one 
• 886584-62-9 4-dimethylamino-4'-(tetrahydro-2H-pyran-2-yloxy)chalcone 
• 16162-69-9 1-(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)ethanone 
• 99-93-4 4-Hydroxyacetophenone 
• 100-10-7 4-dimethylamino-benzaldehyde 
• 100-06-1 1-(4-methoxyphenyl)ethanone 

Downstream Products

• 102178-06-3 (E)-3-(4-(dimethylamino)phenyl)-1-(4-(2-hydroxyethoxy)phenyl)-2-propen-1-one 
• 958456-62-7 (E)-3-(4-(dimethylamino)phenyl)-1-(4-(2-(hydroxyethoxy)ethoxy)phenyl)-2-propen-1-one 
• 958456-64-9 (E)-3-(4-(dimethylamino)phenyl)-1-(4-(2-((hydroxyethoxy)ethoxy)ethoxy)phenyl)-2-propen-1-one 
• 1607465-93-9 (E)-3-(4-(dimethylamino)phenyl)-1-(4-(((E)-3-(tributylstannyl)allyl)oxy)phenyl) prop-2-en-1-one 
• 1607465-96-2 (E)-3-(4-(dimethylamino)phenyl)-1-(4-(((E)-3-iodoallyl)oxy)phenyl)prop-2-en-1-one 

Relevant academic research and scientific papers

68Ga based probe for Alzheimer's disease: Synthesis and preclinical evaluation of homodimeric chalcone in β-amyloid imaging

In an attempt to explore use of PET radioisotope, 68Ga, in the diagnosis of Alzheimer's disease, a metal-based homodimeric ligand exhibiting high affinity towards Aβ aggregates was designed by conjugating two chalcone units with the chelating system, diethylenetriaminepentaacetic acid. Bischalcone derivative, 5,8-bis(carboxymethyl)-13-(4-((E)-3-(4-(dimethylamino) phenyl)acryloyl)phenoxy)-2-(2-(2-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl) phenoxy)ethylamino)-2-oxoethyl)-10-oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid, DT(Ch)2 was synthesized in 95% yield with high purity. It was radiolabelled with 68Ga under mild conditions with 85.4% efficiency and 9.5-10 MBq nmol-1 specific activity. An in vitro binding assay on Aβ42 aggregates displayed high binding affinity of 68Ga-DT(Ch) 2 and inhibition constant of 4.18 ± 0.62 nM. The fluorescent properties of the ligand with peaks of absorption/emission at 410/540 nm exhibited a blue shift with 5.5-fold increase in emission intensity on binding with Aβ aggregates. Blood kinetics of the complex performed on normal rabbit exhibited fast clearance (t1/2(F) = 24 ± 0.08 min; t1/2(S) = 2 h 40 ± 0.04 min). Ex vivo biodistribution analysis demonstrated blood-brain barrier penetration with brain uptake of 1.24 ± 0.31% ID g-1 at 2 min p.i. and rapid washout with negligible activity (0.36% ID g-1) left at 30 min p.i. These preliminary studies reveal that the bivalent approach of synthesis had minimal effect on binding affinity, signifying that the developed 68Ga-complex, 68Ga-DT(Ch)2, may offer a new perspective in generator produced PET imaging probes for Alzheimer's disease. This journal is the Partner Organisations 2014.

Synthesis, spectral and biological studies of new 2-amino-3-cyanopyridine derivatives and their transition metals complexes

In this study, new substituted 2-amino-3-cyanopyridine derivatives were synthesized in excellent yields by reacting chalcone derivatives with malanonitrile in the presence of ammonium acetate, and new complexes with these ligands were synthesized and characterized by elemental analysis, UV, IR, Mass, and NMR (1H, 13C) spectroscopy, and had the general formula: [ML2(H2O)2]Cl2 where M= Co(II), Ni(II) and Cu(II), [ML2(H2O)Cl]Cl2 where M= Cr (III). On the basis of analytical data and IR studies, a 1:2 metal to ligand stoichiometry has been suggested to these coordination complexes. All of these studies suggest that the ligand acted as a bi-dentate ligand when it coordinates with metal ions, and that the prepared complexes had an octahedral geometry coordinated by both the nitrogen of (cyano group) and (amino group). The ligand and its complexes were tested for antimicrobial activity against gram negative (Pseudonomous aeruginosa) and gram positive (Bacillus subtitis) bacteria. All of these complexes have been shown to be more antibacterial than their respective ligands.

Design, synthesis and molecular modelling studies of some pyrazole derivatives as carbonic anhydrase inhibitors

In this study, newly synthesised compounds 6, 8, 10 and other compounds (1–5, 7 and 9) and their inhibitory properties against the human isoforms hCA I and hCA II were reported for the first time. Compounds 1–10 showed effective inhibition profiles with KI values in the range of 5.13–16.9 nM for hCA I and of 11.77–67.39 nM against hCA II, respectively. Molecular docking studies were also performed with Glide XP to get insight into the inhibitory activity and to evaluate the binding modes of the synthesised compounds to hCA I and II. More rigorous binding energy calculations using MM-GBSA protocol which agreed well with observed activities were then performed to improve the docking scores. Results of in silico calculations showed that all compounds obey drug likeness properties. The new compounds reported here might be promising lead compounds for the development of new potent inhibitors as alternatives to classical hCA inhibitors.

Combining chalcones with donepezil to inhibit both cholinesterases and aβ fibril assembly

The fact that the number of people with Alzheimer's disease is increasing, combined with the limited availability of drugs for its treatment, emphasize the need for the development of novel effective therapeutics for treating this brain disorder. Herein, we focus on generating 12 chalcone-donepezil hybrids, with the goal of simultaneously targeting amyloid-β (Aβ) peptides as well as cholinesterases (i.e., acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)). We present the design, synthesis, and biochemical evaluation of these two series of novel 1,3-chalcone-donepezil (15a-15f) or 1,4-chalcone-donepezil (16a-16f) hybrids. We evaluate the relationship between their structures and their ability to inhibit AChE/BChE activity as well as their ability to bind Aβ peptides. We show that several of these novel chalcone-donepezil hybrids can successfully inhibit AChE/BChE as well as the assembly of N-biotinylated Aβ(1-42) oligomers. We also demonstrate that the Aβ binding site of these hybrids differs from that of Pittsburgh Compound B (PIB).

Synthesis, docking studies and: In vitro evaluation of novel chalcones as potent inhibitors of phosphodiesterase 5 from human platelets and 5A from bovine recombinant

A series of new nitric oxide donor chalcone moieties were synthesized and evaluated for phosphodiesterase 5 (PDE 5) and 5A (PDE 5A) inhibition potential from human plasma and bovine recombinant, respectively. Molecular docking showed an excellent binding

Synthesis, biological evaluation, and molecular docking study of some new pyrazoline derivatives as cyclooxygenase-II inhibitors and anti-inflammatory agents

New pyrazoline derivatives bearing chalcone frame were synthesized, characterized, and evaluated for their cyclooxygenase-II (COX-II) inhibitory activity and anti-inflammatory potential. The synthesis of intermediate chalcone derivative was carried out through Claisen-Schmidt reaction between carbonyl compounds while cyclization of chalcone by acetylated hydrazine hydrate offered diaryl pyrazoline moiety. The incorporation of α-β unsaturated keto group (chalcone frame) was achieved through base catalyzed condensation reaction between carbonyl group of N-acetyl pyrazoline and aryl aldehyde. The compound (E)-3-(4-hydroxyphenyl)-1-(3-(4-hydroxyphenyl)-5-phenyl-4,5-dihydropyrazol-1-yl)prop-2-en-1-one (6i) exhibited potent COX-II inhibitory activity. The inhibition of COX-II enzyme was found to be 85.3% for compound 6i and 70.4% for reference standard celecoxib. The carrageenan-induced rat paw edema method was employed to determine in vivo anti-inflammatory potential and 42.41% of inhibition in diameter of rat paw edema was measured for compound 6i. Moreover, molecular docking study was also performed using “Maestro (Schr?dinger) Molecular Docking Software,” and the results of docking study revealed prompt binding interactions between synthesized compound and target receptor. The compound which was found to be most potent one in biological study also exhibited good docking potential in molecular docking study, and hydrogen bond was observed between potent compound 6i and amino acid residue of target protein receptor.

Nonlinear optical studies and structure-activity relationship of chalcone derivatives with in silico insights

Nine chalcones were prepared via Claisen-Schmidt condensation, and characterized by UV–vis, IR1H NMR13C NMR and mass spectrometry. One of the representative member 4-NDM-TC has been studied via single crystal XRD and the TGA/DTA tech

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

A series of new pyrimidine–triazine hybrids (4a–t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED50), 285.02 and 293.42 mg/kg (scPTZ ED50), and 389.11 and 412.16 mg/kg (TD50), respectively. Docking studies were also performed for all synthesized compounds to get insight into the binding pattern toward the GABAA receptor as a possible mechanism of their anticonvulsant action, and in silico ADME studies were carried out to predict the safety and stability of the molecules. The increased GABA level in the experimental animals in the neurochemical estimation assay confirmed their GABAergic modulating activity. The most potent compounds were also evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a broad spectrum of anticonvulsant activity with a large safety margin. Together, this research suggested that 4o and 4s may serve as leads in the discovery and development of new anticonvulsant drugs.

Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship

Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1-10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20-14.38 μM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1-3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic techniques. These findings could lead to design and discover of new tyrosinase inhibitors to control the melanine overproduction and overcome the economic loss of food industry.

Synthesis and evaluation of antiinflammatory activity of substituted chalcone derivatives

In an effort to develop potent antiinflammatory agents, a series of substituted chalcone derivatives was synthesized and evaluated for antiinflammatory activity through monitoring of their ability to inhibit xylene-induced ear edema in mice. Some of the tested compounds exhibited significant activity, and compounds 3f [(E)-1-(2,4-dihydroxyphenyl)-3-(4- dimethylamino)phenyl)prop-2-en-1-one] and 3h [(E)-3-(4-chlorophenyl)-1-(2,4- dihydroxyphenyl)prop-2-en-1-one] showed the highest antiinflammatory activity (62 and 68% inhibition, respectively, 2 h before administration), comparable with or even slightly more potent than the reference drug ibuprofen (53%). Furthermore, the structure-activity relationship of these substituted chalcone derivatives was demonstrated.