108440-16-0

Upstream product

• 118-93-4 o-hydroxyacetophenone 
• 587-04-2 m-Chlorobenzaldehyde 
• 1849-59-8 2-(3'-chlorophenyl)-2,3-dihydro-4H-chromen-4-one 

Downstream Products

• 1849-59-8 2-(3'-chlorophenyl)-2,3-dihydro-4H-chromen-4-one 
• 1849-61-2 3'-Chloroflavone 
• 1657006-96-6 C₁₈H₁₅ClO₂ 
• 1657006-76-2 C₁₈H₁₅Br₂ClO₂ 
• 112980-35-5 (Z)-2-(3-chlorobenzylidene)benzofuran-3(2H)-one 
• 649739-69-5 2,3-dibromo-3-(3-chloro-phenyl)-1-(2-hydroxy-phenyl)-propan-1-one 

Relevant academic research and scientific papers

Anti-inflammatory, analgesic and antipyretic 4,6-disubstituted 3-cyanopyridine-2-ones and 3-cyano-2-aminopyridines

3-Cyano-4-(R,R'-aryl)-6(2-hydroxyphenyl)-2-(1H)pyridones 2a-o and 3-cyano-4-(R-R'-aryl)-6-(2-hydroxyphenyl)-2-aminopyridines were synthesized which showed anti-inflammatory and analgesic activity. Electron withdrawing substituents in 2' or 4' position on

Structure-aided drug development of potential neuraminidase inhibitors against pandemic H1N1 exploring alternate binding mechanism

Abstract: The rate of mutability of pathogenic H1N1 influenza virus is a threat. The emergence of drug resistance to the current competitive inhibitors of neuraminidase, such as oseltamivir and zanamivir, attributes to a need for an alternative approach. The design and synthesis of new analogues with alternate approach are particularly important to identify the potential neuraminidase inhibitors which may not only have better anti-influenza activity but also can withstand challenge of resistance. Five series of scaffolds, namely aurones (1a–1e), pyrimidine analogues (2a–2b), cinnamic acid analogues (3a–3k), chalcones (4a–4h) and cinnamic acid linkages (5a–5c), were designed based on virtual screening against pandemic H1N1 virus. Molecular modelling studies revealed that the designed analogues occupied 430-loop cavity of neuraminidase. Docking of sialic acid in the active site preoccupied with the docked analogues, i.e. in 430-loop cavity, resulted in displacement of sialic acid from its native pose in the catalytic cavity. The favourable analogues were synthesized and evaluated for the cytotoxicity and cytopathic effect inhibition by pandemic H1N1 virus. All the designed analogues resulting in displacement of sialic acid suggested alternate binding mechanism. Overall results indicated that aurones can be measured best among all as potential neuraminidase inhibitor against pandemic H1N1 virus. Graphical abstract: [Figure not available: see fulltext.].

Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines: Topoisomerase I and IIα dual inhibitors with DNA non-intercalative catalytic activity

With the aim to develop novel antiproliferative agents, a new series of eighteen dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines were systematically designed, prepared, and investigated for their topoisomerase (topo) I and IIα inhibitory properties an

Synthesis and biological evaluation of 2-phenol-4-chlorophenyl-6-aryl pyridines as topoisomerase II inhibitors and cytotoxic agents

A new series of 2-phenol-4-chlorophenyl-6-aryl pyridines were designed, synthesized, and evaluated for topoisomerase (topo) I and II inhibitory activities as well as cytotoxic activity against four different human cancer cell lines such as HCT15, T47D, DU

Ruthenium organometallics of chloro-substituted 2′-hydroxychalcones – A story of catecholase biomimetics beyond copper

Four new organoruthenium(II) compounds of 2’-hydroxychalcones, differing in the position of the chloro substituent at chalcone moiety, were prepared by solution synthesis and characterized by chemical analysis, infrared and electron spectroscopy, mass spectrometry and 1D and 2D NMR spectroscopy, as biomimetic functional models of catechol oxidase. The molecular and crystal structures of three compounds were determined by single crystal X-ray diffraction. The organometallics are neutral species having piano-stool pseudo octahedral geometry with ruthenium(II) coordinated by η6-cymene, bidentate monobasic 2’-hydroxychalcone ligand, and chloride ion. The catecholase activity of new organometallics was investigated by electron spectroscopy in three solvents at three temperatures. The kinetic measurements were done under pseudo first order conditions and vmax, kcat, KM, TON, TOF, and Ea values are determined. Compounds (1) – (4) have solvent-dependent catecholase activity with activity decreasing in order ethanol > methanol ? acetonitrile. The highest kcat value and the lowest activation energy were found for the reaction catalyzed by organometallic (4), having a chloro substituent at the B ring of the chalcone ligand in the para position. The kcat values of 104 h?1 and 105 h?1 order at 297 K and 307 K, respectively classify these organometallics among the best artificial functional models of catechol oxidase. The results indicate that the catechol oxidation mediated by organometallics (1) – (4) proceeds via semiquinone radical formation.

Convenient synthesis of flavanone derivatives via oxa-Michael addition using catalytic amount of aqueous cesium fluoride

A total of 36 flavanones, which included polycyclic aromatic and heterocyclic rings, were readily synthesized via oxa-Michael addition from the corresponding hydroxychalcones with a catalytic amount of aqueous cesium fluoride solution under mild conditions. This method could be applied to the scalable synthesis of eriodictyol as a known potent inhibitor of the SARS-CoV-2 spike protein.

Multitarget 2′-hydroxychalcones as potential drugs for the treatment of neurodegenerative disorders and their comorbidities

The complex nature of neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD) calls for multidirectional treatment. Restoring neurotransmitter levels by combined inhibition of cholinesterases (ChEs) and monoamine oxidases (MAOs, MAO-A and MAO-B), in conjunction with strategies to counteract amyloid β (Aβ) aggregation, may constitute a therapeutically strong multi-target approach for the treatment of NDDs. Chalcones are a subgroup of flavonoids with a broad spectrum of biological activity. We report here the synthesis of 2′-hydroxychalcones as MAO-A and MAO-B inhibitors. Compounds 5c (IC50 = 0.031 ± 0.001 μM), 5a (IC50 = 0.084 ± 0.003 μM), 2c (IC50 = 0.095 ± 0.019 μM) and 2a (IC50 = 0.111 ± 0.006 μM) were the most potent, selective and reversible inhibitors of human (h)MAO-B isoform. hMAO-B inhibitors 1a, 2a and 5a also inhibited murine MAO-B in vivo in mouse brain homogenates. Molecular modelling rationalised the binding mode of 2′-hydroxychalcones in the active site of hMAO-B. Additionally, several derivatives inhibited murine acetylcholinesterase (mAChE) (IC50 values from 4.37 ± 0.83 μM to 15.17 ± 6.03 μM) and reduced the aggregation propensity of Aβ. Moreover, some derivatives bound to the benzodiazepine binding site (BDZ-bs) of the γ-aminobutyric acid A (GABAA) receptors (1a and 2a with Ki = 4.9 ± 1.1 μM and 5.0 ± 1.1 μM, respectively), and exerted sedative and/or anxiolytic like effects on mice. The biological results reported here on 2′-hydroxychalcones provide an extension to previous studies on chalcone scaffold and show them as a potential treatment strategy for NDDs and their associated comorbidities.

Stereoselective reduction of flavanones by marine-derived fungi

Biotransformation is an alternative with great potential to modify the structures of natural and synthetic flavonoids. Therefore, the bioreduction of synthetic halogenated flavanones employing marine-derived fungi was described, aiming the synthesis of flavan-4-ols 3a-g with high enantiomeric excesses (ee) of both cis- and trans-diastereoisomers (up to >99% ee). Ten strains were screened for reduction of flavanone 2a in liquid medium and in phosphate buffer solution. The most selective strains Cladosporium sp. CBMAI 1237 and Acremonium sp. CBMAI1676 were employed for reduction of flavanones 2a-g. The fungus Cladosporium sp. CBMAI 1237 presented yields of 72–87% with 0–64% ee cis and 0–30% ee trans with diastereoisomeric ratio (dr) from 52:48 to 64:36 (cis:trans). Whereas Acremonium sp. CBMAI 1676 resulted in 31% yield with 77–99% ee of the cis and 95–99% ee of the trans-diastereoisomers 3a-g with a dr from 54:46 to 96:4 (cis:trans). To our knowledge, this is the first report of the brominated flavon-4-ols 3e and 3f. The use of fungi, with emphasis for these marine-derived strains, is an interesting approach for enantioselective reduction of halogenated flavanones. Therefore, this strategy can be explored to obtain enantioenriched compounds with biological activities.

In quest of small-molecules as potent non-competitive inhibitors against influenza

A series of scaffolds namely aurones, 3-indolinones, 4-quinolones and cinnamic acid-piperazine hybrids, was designed, synthesized and investigated in vitro against influenza A/H1N1pdm09 virus. Designed molecules adopted different binding mode i.e., in 430-cavity of neuraminidase, unlike sialic acid and oseltamivir in molecular docking studies. All molecules reduced the viral titer and exhibited non-cytotoxicity along with cryo-protective property towards MDCK cells. Molecules (Z)-2-(3′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2f), (Z)-2-(4′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2g) and 2-(2′-Methoxy-phenyl)-1H-quinolin-4-one (3a) were the most interesting molecules identified in this research, endowed with robust potencies showing low-nanomolar EC50 values of 4.0 nM, 6.7 nM and 4.9 nM, respectively, compared to reference competitive and non-competitive inhibitors: oseltamivir (EC50 = 12.7 nM) and quercetin (EC50 = 0.56 μM), respectively. Besides, 2f, 2g and 3a exhibited good neuraminidase inhibitory activity in sub-micromolar range (IC50 = 0.52 μM, 3.5 μM, 1.3 μM respectively). Moreover, these molecules were determined as non-competitive inhibitors similar to reference non-competitive inhibitor quercetin unlike reference competitive inhibitor oseltamivir in kinetics studies.

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.