Reaction of nitriles under acidic conditions: a novel, direct formation of condensed 4-chloropyrimidines

From 4 antiplasmodial hit-molecules identified in 2-trichloromethylquinazoline series, we conducted a global Structure-Activity relationship (SAR) study involving 26 compounds and covering 5 molecular regions (I - V), aiming at defining the corresponding pharmacophore and identifying new bioactive derivatives. Thus, after studying the aniline moiety in detail, thienopyrimidine, quinoline and quinoxaline bio-isosters were synthesized and tested on the K1 multi-resistant P. falciparum strain, along with a cytotoxicity evaluation on the human HepG2 cell line, to define selectivity indecies. SARs first showed that thienopyrimidines and quinolines were globally more cytotoxic, while quinoxaline analogs appeared as active as- and less cytotoxic than their quinazoline counterparts. Such pharmacomodulation in quinoxaline series not only provided a new antiplasmodial reference hit-molecule (IC = 0.4 μM, selectivity index = 100), but also highlighted an active (IC = 0.4 μM) and quite selective (SI = 265) synthesis intermediate.

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“…Starting from 4-chloro-2-chloromethylquinazoline [25] 1.1.2. 2-Dichloromethyl-N-(2,4-dichlorophenyl) 1.1.4.…”

Section: -Chloromethyl-n-(24-dichlorophenyl)quinazolin-4-amine (2)mentioning

confidence: 99%

Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold

Desroches

Kieffer

Primas

et al. 2017

European Journal of Medicinal Chemistry

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“…Pyridine containing heterocyclic compounds have extensive pharmacological activities and its derivatives have gained wide acceptance in clinical practice. Similarly 2‐amino‐3‐cyanopyridines have been attracted due to their promising biological activities and also these compounds are useful intermediates to prepare various heterocyclic compounds . Keeping all in mind 2‐amino‐6‐(1, 2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitriles have been recently synthesized by us starting from 3‐acetyl‐4‐hydroxyquinolin‐2(1H)‐one in two‐steps .…”

Section: Introductionmentioning

confidence: 99%

One‐Pot Synthesis of 2‐Amino‐6‐(1,2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitriles Catalysed by NbCl₅ and Their In Vitro Antimicrobial Studies

Krishna

Sarveswari

2019

ChemistrySelect

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Synthesis of 2-amino-6-(1, 2-dihydro-4-hydroxy-2-oxoquinolin-3-yl)-4-arylpyridine-3-carbonitrile has been accomplished via NbCl 5 catalysed multicomponent reaction (MCR). The tested compounds showed better potency than Neomycin and a broad spectrum of antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli. Similarly some of these have showed good activity against Staphylococcus aureus, Klebsiella planticola and Escherichia coli that were comparable to Ciprofloxacin. Also these compounds possess good antifungal activity that was better than Miconazole and comparable to Ciprofloxacin hydrochloride.

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“…Also, they have been identified as novel IKK‐ β inhibitors, A 2A adenosine receptor antagonists and potent inhibitor of HIV‐1 integrase . Moreover, these compounds serve as useful intermediates in preparing a variety of heterocyclic compounds …”

Section: Introductionmentioning

confidence: 99%

Nanomagnetically modified vitamin B₃ (Fe₃O₄@Niacin): An efficient and reusable green biocatalyst for microwave‐assisted rapid synthesis of 2‐amino‐3‐cyanopyridines in aqueous medium

Afradi

Pour

Dolat

et al. 2017

Applied Organom Chemis

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Superparamagnetic nanoparticles of modified vitamin B3 (Fe3O4@Niacin) represent a new, efficient and green biocatalyst for the one‐pot synthesis of 2‐amino‐3‐cyanopyridine derivatives via four‐component condensation reaction between aldehydes, ketones, malononitrile, and ammonium acetate under microwave irradiation in water. This new magnetic organocatalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least six times without significant degradation in the activity. The catalyst was fully characterized by FT‐IR, XRD, SEM, VSM, UV–Vis, DLS and EDS. Excellent yield, very short reaction time (7–10 min), operational simplicity, easy work‐up procedure, avoidance of hazardous or toxic catalysts and organic solvents are the main advantages of this green methodology which makes it more economic than the other conventional methods.

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Reaction of nitriles under acidic conditions: a novel, direct formation of condensed 4-chloropyrimidines

Cited by 53 publications

References 3 publications

Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold

Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold

One‐Pot Synthesis of 2‐Amino‐6‐(1,2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitriles Catalysed by NbCl₅ and Their In Vitro Antimicrobial Studies

Nanomagnetically modified vitamin B₃ (Fe₃O₄@Niacin): An efficient and reusable green biocatalyst for microwave‐assisted rapid synthesis of 2‐amino‐3‐cyanopyridines in aqueous medium

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Reaction of nitriles under acidic conditions: a novel, direct formation of condensed 4-chloropyrimidines

Cited by 53 publications

References 3 publications

Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold

Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold

One‐Pot Synthesis of 2‐Amino‐6‐(1,2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitriles Catalysed by NbCl5 and Their In Vitro Antimicrobial Studies

Nanomagnetically modified vitamin B3 (Fe3O4@Niacin): An efficient and reusable green biocatalyst for microwave‐assisted rapid synthesis of 2‐amino‐3‐cyanopyridines in aqueous medium

Contact Info

Product

Resources

About

One‐Pot Synthesis of 2‐Amino‐6‐(1,2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitriles Catalysed by NbCl₅ and Their In Vitro Antimicrobial Studies

Nanomagnetically modified vitamin B₃ (Fe₃O₄@Niacin): An efficient and reusable green biocatalyst for microwave‐assisted rapid synthesis of 2‐amino‐3‐cyanopyridines in aqueous medium