Synthesis and Antimalarial Activity of 7-Chloro-4-(4-(2-(Oxo, Hydroxyl & Fluoro-2-1 (4-Phenyl)Ethyl)Piperazin-1-yl)Quinoline Derivatives

Since these days, microbes are resistant to the drugs available in the market, which has caused an alarming impact on society. 18 compounds in a series of 7-chloro-4-(piperazin-1-yl)quinoline derivatives were synthesized by nucleophilic addition reaction of piperazine with 4,7-dichloroquinoline followed by phenacyl bromides addition to heteroaryl piperazine and then reduction and fluorination. All 18 compounds were evaluated in vitro for their antimalarial activity against plasmodium falciparum strain. Although 12 compounds showed good activity, compound 3c was found to be more potent than standard drug Quinine having MIC 0.18 μg/ mL. On the other hand, 3d, 3e, 5a, and 5f were found to be equipotent (MIC 0.26 μg/ mL) to the standard drug.

Phenacylation of 6-Methyl-Beta-Nitropyridin-2-Ones and Further Heterocyclization of Products

Reaction between the derivatives of 6-methyl-beta-nitropyridin-2-one and phenacyl bromides was studied, and the yields observed were extremely low. The pyridones were converted via chloropyridines to methoxyderivatives, which were N-phenacylated. N-Phenacyl derivatives of 4,6-dimethyl-5-nitropyridin-2-one under the action of base gave 5-hydroxy-8-nitroindolizine and under acidic conditions gave 5-methyl-6-nitrooxazole[3,2-a]pyridinium salt, which underwent recycization with MeONa to 5-methoxy-8-nitroindolizine.

A Three Component Protocol for the Synthesis of Aziridines using BF3·(OEt)2

Synthesis of N-(1R,2S)-2-(bromo-3-oxo-1,3-diphenylpropyl)-4-methylbenzene sulfonamide and N-(1R,2S)-(2-bromo-3-oxo-1,3-diphenylpropyl)-4-methylbenzene sulfonamide was carried out by a three component reaction using phenacyl bromide, p-toluenesulfonamide and carboxyaldehyde in presence of mild Lewis acid such as BF3·(OEt)2 in dichloromethane. The synthetic utility of this protocol was carried out with syn-isomer to yield corresponding cis-aziridines. This protocol was operationally simple for a wide variety of substituted carboxaldehydes and substituted phenacyl bromides.

Synthesis and anticonvulsant activity of 6-methyl-2-((2-oxo-2-arylethyl)thio)pyrimidin-4(3 H)-one derivatives and products of their cyclization

The alkylation of 6-methyl-2-thioxo-2,3-dihydro-1H-pyrimidine-4-one phenacyl bromides under different conditions was investigated. It was found that during the reaction in the medium of DMF/K2CO3 a mixture of 2-(2-aryl-2-oxoethyl)thio-6-methyl-pyrimidine-4(3H)-one and 3-hydroxy-3-aryl-7-methyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-5-one was formed. The holding of the resulting mixture in the concentrated sulphuric acid leads to the formation of cyclization products - derivatives of 3-aryl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one with high yields. Individual S-alkylated derivatives – 2-(2-aryl-2-oxoethyl)thio-6-methyl-pyrimidine-4(3H)-one - were obtained by reacting in methanol in the presence of sodium methoxide. Pharmacological screening of synthesized compounds for anticonvulsant activity on the model of pentylenetetrazole seizures in rats was carried out and some regularity “structure-activity” was established.

Schiff Bases and Triazolothiadiazines Derived from A Thiophene-Substituted 4-Amino-3-Mercapto-1,2,4-Triazole

4-Amino-5-(thiophen-2-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione was synthesized and converted into the corresponding Schiff bases using several aromatic aldehydes. Reaction of this aminotriazolethione with phenacyl bromides lead to triazolothiadiazines, which were subsequently reduced with NaBH4 to dihydrotriazolothiadiazines. The latter type of fused heterocycle has been also obtained directly by reacting one of the previously obtained Schiff base with phenacyl bromides. NMR analysis confirmed the structures of the synthesized compounds.

Synthesis and Pancreatic Lipase Inhibitory Activity of Phenacyl Esters of N-Aroyl Amino Acids

Background: Obesity has become a major life-threatening disorder as it is associated with many risk factors such as coronary heart disease, hypertension, type II diabetes and certain forms of cancer. Pancreatic lipase inhibition is one of the alternate strategies to treat obesity. In our previous study, phenacyl ester of N-sulphonyl beta alanine was obtained as a hit molecule when pharmacophore- based virtual screening was carried out using reported pancreatic lipase inhibitors. Objective: In search of novel pancreatic lipase inhibitors, three series of phenacyl esters of Nsubstituted amino acids were synthesized and evaluated for their pancreatic lipase inhibitory activity. Methods: N-aroylation of amino acids and subsequent esterification with different phenacyl bromides in the presence of N,N-Dimethylformamide (DMF) afforded the corresponding phenacyl esters in quantitative yields. Results: The synthesized compounds were found to have good pancreatic lipase inhibitory activity and showed IC50 in the range of 0.036 and 84 μg/ml. Conclusion: All the synthesized compounds showed better pancreatic lipase inhibitory activity and it indicates that the N-aroylated phenacyl esters could be considered as lead moiety for further studies to develop novel anti-obesity potentials.

Facile synthesis of 2-arylimidazo[1,2-a]pyridines catalysed by DBU in aqueous ethanol

A facile protocol for the synthesis of 2-arylimidazo[1,2-a]pyridines was developed using two-component cyclization of substituted 2-aminopyridines and substituted phenacyl bromides in 65–94% yield. The reaction was DBU catalysed using green solvent, aqueous ethanol (1 : 1 v/v) at room temperature. The atom economy of the products was calculated to be 66.25–73.41%. The developed protocol successfully exhibits a broad substrate scope, less reaction time, high to moderate yield and multigram scale synthesis.

Ultrasound Aided Expedient Synthesis, Characterization and Antimicrobial Studies of Fluorenyl-Hydrazono-Thiazole Derivatives

Ultrasound assisted facile synthesis of fluorenyl-hydrazonothiazoles (4a-d) in quantitative yields by the condensation of 2-(9H-fluoren-9-ylidene)hydrazinecarbothioamide (2) with substituted phenacyl bromides in presence of dimethyl formamide has been reported. The reaction of carbothioamide 2 with α-haloacids resulted in to fluorenyl-hydrazonothiazolidin-4-ones (3). The structural characterization of the cyclized products have been established by elemental analysis and spectral data (IR, NMR and mass). The antimicrobial studies of the synthesized compounds are also reported.

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

An efficient, simple, and metal-free synthetic approach for the N- and O-benzoylation of various amines/benzyl alcohols with pyridinium salts of phenacyl bromides is demonstrated to generate the corresponding amides and esters. This protocol facilitates the oxidative cleavage of a C–C bond followed by formation of a new C–N/C–O bond in the presence of K2CO3. Various pyridinium salts of phenacyl bromides can be readily transformed into a variety of amides and esters which is an alternative method for the conventional amidation and esterification in organic synthesis. High functional group tolerance, broad substrate scope and operational simplicity are the prominent advantages of the current protocol.