36136-61-5

Upstream product

• 89-98-5 2-chloro-benzaldehyde 
• 118-93-4 o-hydroxyacetophenone 

Downstream Products

• 610277-48-0 2-(5-(2-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol 
• 116115-48-1 2'-Chloroflavone 
• 6344-24-7 2,3-dihydro-2-(2,-chlorophenyl)-4H-1-benzopyran-4-one 
• 6344-24-7 (S)-2-(2-chlorophenyl)chroman-4-one 
• 1431881-31-0 ethyl 5-amino-4-((1-(2-chlorophenyl)-3-(2-hydroxyphenyl)-3-oxopropyl)sulfanyl)benzo[b]thiophene-2-carboxylate 
• 61370-64-7 2-(2-chlorobenzylidene)benzofuran-3(2H)-one 

Relevant academic research and scientific papers

Monoamine oxidase inhibitory activity of 2-aryl-4H-chromen-4-ones

A series of twenty 2-aryl-4H-chromen-4-one (flavones) derivatives (3a-3s) were synthesized and tested for hMAO inhibitory activity. Fifteen compounds (3a, 3c, 3e-3h, 3j-3p, 3r, 3s) were found to be selective towards MAO-B, while 3d was selective towards MAO-A, and 3b, 3i and 3q were non-selective. Experimental Selectivity Index for MAO-B ranges from 2.0 (3g, 3p) to 30.0 (3j). Compound 3j, which is carrying 3,4-di-OMeC6H3 groups at R position on the molecule, was found to be potent MAO-B inhibitor amongst the fifteen with Ki value for MAO-B of 0.16 ± 0.01 μM comparable to that of standard drug, Selegiline (Ki for MAO-B is 0.16 ± 0.01 μM). Compound 3j also appeared as the most selective MAO-B inhibitor according to its best selectivity index (30.0), which is comparable to that of Selegiline (SIMAO-B = 35.0). Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.0 and Amber12 to understand the molecular level interaction and energy relation of MAO isoforms with selective inhibitors (3d and 3j). Simulation results are in good agreement with the experimental results. Leads identified may further be explored to develop potent isoform specific inhibitors of MAO.

Glycolytic inhibition and antidiabetic activity on synthesized flavanone scaffolds with computer aided drug designing tools

Background: Diabetes mellitus is a challengeable metabolic disorder that leads to a group of complications when the HbA1c level is not maintained. Most of the existing drugs avail-able in the market in long-term use may lead to serious adverse effects. He

Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition

In this study, we have designed and synthesized pyrazoline analogues that partially mimic the structure of mycobactin, to address the requirement of novel therapeutics to tackle the emerging global challenge of antimicrobial resistance (AMR). Our investigation resulted in the identification of novel lead compounds 44 and 49 as potential mycobactin biosynthesis inhibitors against mycobacteria. Moreover, candidates efficiently eradicated intracellularly surviving mycobacteria. Thermofluorimetric analysis and molecular dynamics simulations suggested that compounds 44 and 49 bind to salicyl-AMP ligase (MbtA), a key enzyme in the mycobactin biosynthetic pathway. To the best of our knowledge, these are the first rationally designed mycobactin inhibitors to demonstrate an excellent in vivo pharmacokinetic profile. In addition, these compounds also exhibited more potent whole-cell efflux pump inhibition than known efflux pump inhibitors verapamil and chlorpromazine. Results from this study pave the way for the development of 3-(2-hydroxyphenyl)-5-(aryl)-pyrazolines as a new weapon against superbug-associated AMR challenges.

Chloro and bromo-pyrazole curcumin Knoevenagel condensates augmented anticancer activity against human cervical cancer cells: design, synthesis, in silico docking and in vitro cytotoxicity analysis

With an endeavor to develop novel curcumin analogs as potential anti-cancer agents, we designed and synthesized a series of Knoevenagel condensates by clubbing pyrazole carbaldehydes at the active methylene carbon atom of the curcumin backbone. Molecular docking studies were carried out to target the proposed derivatives on human kinase β (IKKβ), a potential anti-cancer target. The chloro derivative displayed five hydrogen bond interactions with a docking score of ?11.874 kcal/mol higher than curcumin (docking score = ?7.434 kcal/mol). This was supported by the fact that the propellant shaped derivatives fitted aptly into the binding pocket. Molecular simulations studies were also conducted on the lead molecule and the results figured out that the stable complexes were developed as the minimal deviations per residue of protein within the range of 0.11–0.92 ?. The screened compounds were synthesized, characterized and evaluated in vitro for cytotoxicity against cervical cancer cell line, HeLa using standard cell proliferation assay. Chloro derivative and bromo analog demonstrated IC50 (half maximal inhibitory concentration) value of 14.2 and 18.6 μg/ml, respectively, significantly lower than 42.4 μg/ml of curcumin and higher than 0.008 μg/ml of paclitaxel. Induction of apoptosis was evaluated in the terms of cleavage of caspase-3 enzyme and they also exhibited 69.6 and 65.4% of apoptosis significantly higher than 19.9% induced by curcumin. In conclusion, chloro and bromo derivatives must be evaluated under a set of stringent in vitro and in vivo parameters for translating in to a clinically viable product. Communicated by Ramaswamy H. Sarma.

Design, synthesis and biological evaluation of substituted flavones and aurones as potential anti-influenza agents

We designed a series of substituted flavones and aurones as non-competitive H1N1 neuraminidase (NA) inhibitors and anti-influenza agents. The molecular docking studies showed that the designed flavones and aurones occupied 150-cavity and 430-cavity of H1N1-NA. We then synthesized these compounds and evaluated these for cytotoxicity, reduction in H1N1 virus yield, H1N1-NA inhibition and kinetics of inhibition. The virus yield reduction assay and H1N1-NA inhibition assay demonstrated that the compound 1f (4-methoxyflavone) had the lowest EC50 of 9.36 nM and IC50 of 8.74 μM respectively. Moreover, kinetic studies illustrated that compounds 1f and 2f had non-competitive inhibition mechanism.

Chiral Hydroxytetraphenylene-Boron Complex Catalyzed Asymmetric Diels-Alder Cycloaddition of 2′-Hydroxychalcones

(S)-2,15-Cl2-DHTP-boron complex catalyst for the asymmetric Diels-Alder cycloaddition of 2′-hydroxychalcones and dienes was developed and tested. The resulting cyclohexenes with three chiral centers were obtained in high yields (up to 98%) with excellent stereoselectivities (up to >20:1 endo/exo, >99% ee). This catalytic system features high efficiency, broad substrate scopes, and mild reaction conditions. In addition, a DFT study was performed to explain the stereochemical course of the asymmetric induction.

Synthesis and kinetic investigations for the isomerization process of 2–hydroxy chalcone derivatives

The wide biological activities of flavanones are mainly depends on their physical and chemical properties, thus a number of substituted 2-Hydroxy chalcones have been synthesized, and their isomerization to their corresponding flavanones was studied. In order to determine the rate constant, kinetic experiments were performed using HPLC technique in (9:1) (CH3CN:H2O) medium at different temperature (298-318) K. The obtained results were interpreted by four steps mechanism, which considered the existence of phenoxide ion as the key intermediate. This study performed with a pseudo first order (reaction in which the rate for the studied compounds follow the sequence 5 > 2 > 1 > 4 > 3, the activation energy have the same sequence for these compounds .The effect of substituents on the rate showed that electronic and steric factors play reasonable role on the stability of the product .

Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi

Chagas disease is caused by infection with the parasite protozoan Trypanosoma cruzi and affects about 8 million people in 21 countries in Latin America. The main form of treatment of this disease is still based on the use of two drugs, benznidazole and nifurtimox, which both present low cure rates in the chronic phase and often have serious side-effects. Herein, we describe the synthesis of tricyclic coumarins that were obtained via NHC organocatalysis and evaluation of their trypanocidal activity. Molecular docking studies against trypanosomal enzyme triosephosphate isomerase (TIM) were carried out, as well as a theoretical study of the physicochemical parameters. The tricyclic coumarins were tested in vitro against the intracellular forms of Trypanosoma cruzi. Among the 18 compounds tested, 10 were more active than the reference drug benznidazole. The trypanocidal activity of the lead compound was rationalized by molecular docking study which suggested the strong interaction with the enzyme TIM by T.?cruzi and therefore indicating a possible mode of action. Furthermore, the selectivity index of eight tricyclic coumarins with high anti-T.?cruzi activity was above 50 and thus showing that these lead compounds are viable candidates for further in vivo assays.

Synthesis of 3-HCF2S-Chromones through Tandem Oxa-Michael Addition and Oxidative Difluoromethylthiolation

A simple protocol for the synthesis of difluoromethylthiolated chromen-4-ones using elemental sulfur and ClCF2CO2Na as the difluoromethylthiolating agent is described. Three-component reactions of 2′-hydroxychalcones, ClCF2CO2Na, and sulfur under basic conditions using TEMPO as the oxidant afforded HCF2S-containing 4H-chromen-4-one and 9H-thieno[3,2-b]chromen-9-one derivatives in good yield. The protocol is practical and efficient, and the starting materials are cheap and readily available.

Design, synthesis, biological evaluation, structure-activity relationship study, and mode of action of 2-phenol-4,6-dichlorophenyl-pyridines

Human DNA topoisomerases (Topos) are essential nuclear enzyme whose level of expression is potential indicator for prediction of responsive result of chemotherapy. Topos has become a key cellular target for most of the anticancer agents that regulates top