- Reaction of N-arylcarbamoyl-1,4-benzoquinone imines with sodium arenesulfinates
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N-Arylcarbamoyl-1,4-benzoquinone imines possessing at least one free ortho position with respect to the carbonyl carbon atom in the quinoid ring react with sodium arenesulfinates according to the nucleophilic 1,4-addition pattern with complete regioselect
- Konovalova,Avdeenko,Sergeeva,Menafova
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- Green and efficient synthesis of thioureas, ureas, primary: O -thiocarbamates, and carbamates in deep eutectic solvent/catalyst systems using thiourea and urea
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An efficient and general catalysis process was developed for the direct preparation of various primary O-thiocarbamates/carbamates as well as monosubstituted thioureas/ureas by using thiourea/urea as biocompatible thiocarbonyl (carbonyl) sources. This procedure used choline chloride/tin(ii) chloride [ChCl][SnCl2]2 with a dual role as a green catalyst and reaction medium to afford the desired products in moderate to excellent yields. Moreover, the DES can be easily recovered and reused for seven cycles with no significant loss in its activity. Besides, the method shows very good performance for synthesizing the desired products on a large scale.
- Bagherzadeh, Nastaran,Sardarian, Ali Reza,Inaloo, Iman Dindarloo
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supporting information
p. 11852 - 11858
(2021/07/12)
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- Synthesis of Five-Membered Cyclic Guanidines via Cascade [3 + 2] Cycloaddition of α-Haloamides with Organo-cyanamides
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The convenient preparation of N2-unprotected five-membered cyclic guanidines was achieved through a cascade [3 + 2] cycloaddition between organo-cyanamides and α-haloamides under mild conditions in good to excellent yields (up to 99%). The corresponding cyclic guanidines could be easily transformed into hydantoins via hydrolysis.
- Wang, Chuan-Chuan,Qu, Ya-Li,Liu, Xue-Hua,Ma, Zhi-Wei,Yang, Bo,Liu, Zhi-Jing,Chen, Xiao-Pei,Chen, Ya-Jing
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p. 3546 - 3554
(2021/02/16)
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- A Straightforward Synthesis of N-Substituted Ureas from Primary Amides
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A direct and convenient method for the preparation of N-substituted ureas is achieved by treating primary amides with phenyliodine diacetate (PIDA) in the presence of an ammonia source (NH 3 or ammonium carbamate) in MeOH. The use of 2,2,2-trifluoroethanol (TFE) as the solvent increases the electrophilicity of the hypervalent iodine species and allows the synthesis of electron-poor carboxamides. This transformation involves a nucleophilic addition of ammonia on the isocyanate intermediate generated in situ by a Hofmann rearrangement of the starting amide.
- Franck, Xavier,Glachet, Thomas,Ibert, Quentin,Lohier, Jean-Fran?ois,Reboul, Vincent,Saraiva Rosa, Nathalie
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p. 2099 - 2105
(2020/07/13)
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- Dual palladium-photoredox catalyzed chemoselective C-H arylation of phenylureas
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A highly chemoselective C-H arylation of phenylureas has been accomplished using dual palladium-photoredox catalysis at room temperature without any additives, base or external oxidants. Regioselective C-H arylation ofN,N'-diaryl substituted unsymmetrical phenylureas has also been accomplished by a careful choice of aryl groups.
- Babu, Sakamuri Sarath,Shahid,Gopinath, Purushothaman
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supporting information
p. 5985 - 5988
(2020/06/04)
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- Catalytic hydration of cyanamides with phosphinous acid-based ruthenium(ii) and osmium(ii) complexes: scope and mechanistic insights
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The synthesis of a large variety of ureas R1R2NC(O)NH2 (R1 and R2 = alkyl, aryl or H; 26 examples) was successfully accomplished by hydration of the corresponding cyanamides R1R2NCN using the phosphinous acid-based complexes [MCl2(η6-p-cymene)(PMe2OH)] (M = Ru (1), Os (2)) as catalysts. The reactions proceeded cleanly under mild conditions (40-70 °C), in the absence of any additive, employing low metal loadings (1 molpercent) and water as the sole solvent. In almost all the cases, the osmium complex 2 featured a superior reactivity in comparison to that of its ruthenium counterpart 1. In addition, for both catalysts, the reaction rates observed for the hydration of the cyanamide substrates were remarkably faster than those involving classical aliphatic and aromatic nitriles. Computational studies allowed us to rationalize all these trends. Thus, the calculations indicated that the presence of a nitrogen atom directly linked to the CN bond depopulates electronically the nitrile carbon by inductive effect when coordinated to the metal center, thus favouring the intramolecular nucleophilic attack of the OH group of the phosphinous acid ligand to this carbon. On the other hand, the higher reactivity of Os vs. Ru seems to be related with the lower ring strain on the incipient metallacycle that starts to form in the transition state associated with this key step in the catalytic cycle. Indirect experimental evidence of the generation of the metallacyclic intermediates was obtained by studying the reactivity of [RuCl2(η6-p-cymene)(PMe2OH)] (1) towards dimethylcyanamide in methanol and ethanol. The reactions afforded compounds [RuCl(η6-p-cymene)(PMe2OR)(NCNMe2)][SbF6] (R = Me (5a), Et (5b)), resulting from the alcoholysis of the metallacycle, which could be characterized by single-crystal X-ray diffraction. This journal is
- álvarez, Daniel,Cadierno, Victorio,Crochet, Pascale,González-Fernández, Rebeca,López, Ramón,Menéndez, M. Isabel
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p. 4084 - 4098
(2020/07/09)
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- Direct conversion of carboxylic acids to various nitrogen-containing compounds in the one-pot exploiting curtius rearrangement
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Herein we report, a single-pot multistep conversion of inactivated carboxylic acids to various N-containing compounds using a common synthetic methodology. The developed methodology rendered the use of carboxylic acids as a direct surrogate of primary amines, for the synthesis of primary ureas, secondary/tertiary ureas, O/S-carbamates, benzoyl ureas, amides, and N-formyls, exploiting the Curtius reaction. This approach has a potential to provide a diversified library of N-containing compounds, starting from a single carboxylic acid, based on the selection of the nucleophile.
- Kumar, Arun,Kumar, Naveen,Sharma, Ritika,Bhargava, Gaurav,Mahajan, Dinesh
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p. 11323 - 11334
(2019/09/10)
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- Design and Synthesis of Iminosydnones for Fast Click and Release Reactions with Cycloalkynes
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Emerging applications in the field of chemical biology are currently limited by the lack of bioorthogonal reactions allowing both removal and linkage of chemical entities on complex biomolecules. We recently discovered a novel reaction between iminosydnones and strained alkynes leading to two products resulting from ligation and fragmentation of iminosydnones under physiological conditions. We now report the synthesis of a panel of substituted iminosydnones and the structure reactivity relationship between these compounds and strained alkyne partners. This study identified the most relevant substituents, which allow to increase the rate of the transformation and to develop a bifunctional cleavable linker with improved kinetics.
- Riomet, Margaux,Decuypere, Elodie,Porte, Karine,Bernard, Sabrina,Plougastel, Lucie,Kolodych, Sergii,Audisio, Davide,Taran, Frédéric
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supporting information
p. 8535 - 8541
(2018/05/30)
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- Superparamagnetic Fe3O4 Nanoparticles in a Deep Eutectic Solvent: An Efficient and Recyclable Catalytic System for the Synthesis of Primary Carbamates and Monosubstituted Ureas
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Superparamagnetic Fe3O4 nanoparticles were used to synthesize various primary carbamates as well as monosubstituted and N,N-disubstituted ureas. This efficient phosgene-free process used urea as an eco-friendly carbonyl source in the presence of a biocompatible deep eutectic solvent (DES) to provide an inexpensive and attractive route that afforded the products in moderate to excellent yields. The employed DES serves both a catalytic role and as the green reaction medium. The magnetic nanocatalyst and DES can been reused several times without a significant loss of activity.
- Inaloo, Iman Dindarloo,Majnooni, Sahar,Esmaeilpour, Mohsen
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p. 3481 - 3488
(2018/07/29)
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- Optimization of 5-arylidene barbiturates as potent, selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia
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Histone lysine specific demethylase 1 (LSD1) is overexpressed in diverse hematologic disorders and recognized as a promising target for blood medicines. In this study, molecular docking-based virtual screening united with bioevaluation was utilized to identify novel skeleton of 5-arylidene barbiturate as small-molecule inhibitors of LSD1. Among the synthesized derivatives, 12a exhibited reversible and potent inhibition (IC50 = 0.41 μM) and high selectivity over the MAO-A and MAO-B. Notably, 12a strongly induced differentiation effect on acute promyelocytic leukemia NB4 cell line and distinctly escalated the methylation level on histone 3 lysine 4 (H3K4). Our findings indicate that 5-arylidene barbiturate may represent a new skeleton of LSD1 inhibitors and 12a deserve as a promising agent for the further research.
- Xu, Siyuan,Zhou, Chen,Liu, Rongfeng,Zhu, Qihua,Xu, Yungen,Lan, Fei,Zha, Xiaoming
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p. 4871 - 4880
(2018/09/22)
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- A green and facile approach for the synthesis of N-monosubstituted ureas in water: Pd catalyzed reaction of arylcyanamides (an unexpected behavior of electron withdrawing groups)
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The Fe3O4 magnetic nano-particles were prepared, coated with tetraethyl orthosilicate (TEOS), functionalized with 3-chloropropyltrimethoxysilane (CPTMS), further functionalized with 2,2′-(piperazine-1,4-diylbis(methylene) dianiline (PDMD) and the corresponding Pd complex synthesized as a novel nano-magnetic heterogeneous catalyst (Fe3O4@SiO2@CPTMS@PDMD@Pd) to be used for the synthesis of various N-monosubstituted ureas in water. Also, in another attempt to see the effect of HCOOH, the hydration reaction of arylcyanamide was carried out in the presence of HCOOH (water + 98% HCOOH) which had two effects: it decreased the amount of the Pd catalyst from 40 to 30 mg, and the reaction condition was changed from the reflux condition to room temperature. Interestingly, the arylcyanamides with electron withdrawing groups influence the course of the reaction and need more reaction times for completion which is an unexpected behavior, probably due to the high electron density around the central carbon atom of the nitrile group.
- Habibi, Davood,Heydari, Somayyeh,Faraji, Alireza,Keypour, Hasan,Mahmoudabadi, Masoumeh
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p. 520 - 529
(2018/06/26)
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- Synthesis and Reactivity of N-Allenyl Cyanamides
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N-Allenyl cyanamides have been accessed via a one-pot deoxycyanamidation-isomerization approach using propargyl alcohol and N-cyano-N-phenyl-p-methylbenzenesulfonamide. The utility of this novel class of allenamide was explored through derivatization, with hydroarylation, hydroamination, and cycloaddition protocols employed to access an array of cyanamide products that would be challenging to access using existing methods.
- Ayres, James N.,Williams, Matthew T.J.,Tizzard, Graham J.,Coles, Simon J.,Ling, Kenneth B.,Morrill, Louis C.
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supporting information
p. 5282 - 5285
(2018/09/13)
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- Design and synthesis of novel N-(4-(Pyridin-2-yloxy)benzylidene)-4-[4-(substituted)phenyl]semicarbazides as potential anticonvulsant agents
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A new series of N-(4-(pyridin-2-yloxy)benzylidene)-4-[4-(substituted)phenyl]semicarbazides (PSSD1-8) were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for their possible anticonvulsant activity. All the derivatives were synthesized by the given scheme and reaction process was monitored by thin layer chromatography. The structure of synthesized derivatives was confirmed by FT-IR, 1H NMR, mass spectroscopy and elemental analysis. The anticonvulsant activity was established after intraperitoneal administration in MES and scMET seizure models. The most active compound of the series was 1-(4-(pyridin-2-yloxy)-benzylidene)-4-p-tolylsemicarbazide (PSSD5). A molecular docking study was carried out in order to assess the interaction and binding modes with target receptor/enzyme. Titled compounds were found to strongly bind to human gamma-aminobutyric acid receptor (GABAAR-β3). A computational study was also carried to predict the pharmacokinetic properties of the synthesized compounds.
- Singh, Prem,Tripathi, Laxmi
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p. 2193 - 2200
(2018/09/10)
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- Bioorthogonal Click and Release Reaction of Iminosydnones with Cycloalkynes
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We report the discovery of a new bioorthogonal click-and-release reaction involving iminosydnones and strained alkynes. This transformation leads to two products resulting from the ligation and fragmentation of iminosydnones under physiological conditions. Optimized iminosydnones were successfully used to design innovative cleavable linkers for protein modification, thus opening up new areas in the fields of drug release and target-fishing applications. This click-and-release technology offers the possibility of exchanging tags on proteins for functionalized cyclooctynes under mild and bioorthogonal conditions.
- Bernard, Sabrina,Audisio, Davide,Riomet, Margaux,Bregant, Sarah,Sallustrau, Antoine,Plougastel, Lucie,Decuypere, Elodie,Gabillet, Sandra,Kumar, Ramar Arun,Elyian, Jijy,Trinh, Minh Nguyet,Koniev, Oleksandr,Wagner, Alain,Kolodych, Sergii,Taran, Frédéric
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supporting information
p. 15612 - 15616
(2017/12/02)
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- Deoxycyanamidation of Alcohols with N-Cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS)
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The first one-pot deoxycyanamidation of alcohols has been developed using N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as both a sulfonyl transfer reagent and a cyanamide source, accessing a diverse range of tertiary cyanamides in excellent isolated yields. This approach exploits the underdeveloped desulfonylative (N-S bond cleavage) reactivity pathway of NCTS, which is more commonly employed for electrophilic C- and N-cyanation processes.
- Ayres, James N.,Ashford, Matthew W.,St?ckl, Yannick,Prudhomme, Vassili,Ling, Kenneth B.,Platts, James A.,Morrill, Louis C.
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supporting information
p. 3835 - 3838
(2017/07/26)
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- Selective and facile oxidative desulfurization of thioureas and thiobarbituric acids with singlet molecular oxygen generated from trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane
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An efficient and facile procedure using trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane has been developed for oxidative desulfurization of thioureas and thiobarbituric acids. The reactions proceeded smoothly very fast under mild conditions in basic media at room temperature to afford the respective ureas in excellent yields. Simple procedure and work up, mild conditions, high yields, short reaction times, use of highly potent and non-toxic oxidant are the main merits of the present method.
- Azarifar, Davood,Golbaghi, Maryam
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- 4-Dodecylbenzenesulfonic acid (DBSA) promoted solvent-free diversity-oriented synthesis of primary carbamates, S-thiocarbamates and ureas
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A simple and highly efficient solvent-free method for the conversion of alcohols, phenols, thiols and amines to primary carbamates, S-thiocarbamates and ureas in the presence of 4-dodecylbenzenesulfonic acid (DBSA) as a cheap and green Bronsted acid reagent has been described. All products were obtained in good to excellent yields and characterized using FT-IR, 1H- and 13C-NMR, MS and CHNS techniques.
- Sardarian, Ali Reza,Inaloo, Iman Dindarloo
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p. 76626 - 76641
(2015/09/22)
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- One-Pot Synthesis of N-Monosubstituted Ureas from Nitriles via Tiemann Rearrangement
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Amidoximes, obtained from the reaction of nitriles with hydroxylamine, underwent Tiemann rearrangement in the presence of benzenesulfonyl chlorides (TsCl or o-NsCl) to form the N-substituted cyanamides. Subsequently, acidic hydrolysis of the cyanamides afforded the corresponding N-monosubstituted ureas. The synthesis of N-monosubstituted ureas from nitriles was accomplished by three steps in one pot, which provides a direct access to versatile N-monosubstituted urea derivatives from a wide variety of nitriles.
- Wang, Chien-Hong,Hsieh, Tsung-Han,Lin, Chia-Chi,Yeh, Wen-Hsiung,Lin, Chih-An,Chien, Tun-Cheng
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p. 1823 - 1826
(2015/08/06)
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- Design and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives bearing an imidazolone moiety as c-Met kinase inhibitors
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A series of 4-(2-fluorophenoxy)quinoline derivatives containing an imidazolone moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, H460, HT-29 and MKN-45). Most compounds showed moderate to excellent activities in enzyme and cellular assays. The most promising analog, 58 (c-Met IC50 = 1.42 nM), displayed 2.1-, 8.6-fold increase against H460, and MKN-45 cell lines, respectively, compared with foretinib. An analysis of structure-activity relationships revealed that an ortho substituted phenyl ring as well as an N-unsubstituted imidazolone linker is favorable for antitumor activity.
- Liao, Weike,Hu, Gang,Guo, Zhuang,Sun, Deyu,Zhang, Lixia,Bu, Yanxin,Li, Yingxiu,Liu, Yajing,Gong, Ping
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p. 4410 - 4422
(2015/08/03)
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- Hybrid Pd/Fe3O4 nanowires: Fabrication, characterization, optical properties and application as magnetically reusable catalyst for the synthesis of N-monosubstituted ureas under ligand-free conditions
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This paper reports the synthesis and use of Pd/Fe3O4 nanowires, as magnetically separable catalysts for ligand-free amidation coupling reactions of aryl halides with benzylurea under microwave irradiation. Then, the in situ hydrogenolysis of the products was performed to afford the N-monosubstituted ureas from good to excellent yields. This method has the advantages of high yields, simple methodology and easy work up. The catalyst can be recovered by using a magnet and reused several times without significant loss of its catalytic activity. The catalyst was characterized using the powder XRD, SEM, EDS and UV-vis spectroscopy. Experimental absorbance spectra was compared with results from the Gans theory.
- Nasrollahzadeh, Mahmoud,Azarian, Abbas,Ehsani, Ali,Sajadi, S.Mohammad,Babaei, Ferydon
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p. 168 - 175
(2014/05/20)
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- Oxidation of phenylthioureas by cetyltrimethylammonium permanganate: A kinetic study
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Phenylthioureas have been subjected to oxidation in acetonitrile medium in neutral condition to investigate the oxidation behaviour of cetyltrimethylammonium permanganate on multifunctional groups. The oxidation product in each reaction is found to be the corresponding phenylurea. The rate of reaction is dependent on [CTAP], [phenylthiourea], [surfactant] and reaction temperature. A Michaelis-Menten type kinetics is observed with respect to the substrate. A reaction mechanism involving the formation of a cyclic intermediate in the slow step is proposed for the oxidation reaction.
- Sahoo, Prangya Rani,Mishra, Bijay K.
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p. 174 - 178
(2014/03/21)
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- Green synthesis, optical properties and catalytic activity of silver nanoparticles in the synthesis of N-monosubstituted ureas in water
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We report the green synthesis of silver nanoparticles by using Euphorbia condylocarpa M. bieb root extract for the synthesis of N-monosubstituted ureas in water. UV-visible studies show the absorption band at 420 nm due to surface plasmon resonance (SPR) of the silver nanoparticles. This reveals the reduction of silver ions (Ag+) to silver (Ago) which indicates the formation of silver nanoparticles (Ag NPs). This method has the advantages of high yields, simple methodology and easy work up.
- Nasrollahzadeh, Mahmoud,Babaei, Ferydon,Mohammad Sajadi,Ehsani, Ali
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p. 423 - 429
(2014/06/23)
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- Synthesis of N-arylureas in water and their N-arylation with aryl halides using copper nanoparticles loaded on natural Natrolite zeolite under ligand-free conditions
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A new method for the synthesis of N-arylureas and their N-arylation with aryl halides has been developed using copper nanoparticles supported on natural Natrolite zeolite as a reusable heterogeneous catalyst under ligand-free conditions.
- Nasrollahzadeh, Mahmoud,Enayati, Mojtaba,Khalaj, Mehdi
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p. 26264 - 26270
(2014/07/08)
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- Discovery of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety as c-Met kinase inhibitors
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A series of novel quinoline derivatives bearing 5-(aminomethylene) pyrimidine-2,4,6-trione moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 45 (c-Met half-maximal inhibitory concentration [IC50] = 1.15 nM) showing high selectivity versus 5 other tyrosine kinases, VEGFR-2, Flt-3, PDGFR-β, c-Kit, and EGFR. Structure-activity relationship studies indicated that electron-donating groups on the phenyl ring at the 3-position of pyrimidine-2,4,6-trione were required to increase the electron density on the 5-(aminomethylene)pyrimidine-2,4,6-trione moiety.
- Tang, Qidong,Zhang, Guogang,Du, Xinming,Zhu, Wufu,Li, Ruijuan,Lin, Huafang,Li, Pengcheng,Cheng, Maosheng,Gong, Ping,Zhao, Yanfang
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p. 1236 - 1249
(2014/03/21)
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- Synthesis and crystal structure of N-(3-benzylamino-2-cyano-3- methylthioacrylyl)-N′-(substituted phenyl)ureas
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Phenylurea groups were introduced into the frame of traditional cyanoacrylate and a series of N-(3-benzylamino-2-cyano-3-methylthioacrylyl)- N′-(substituted phenyl)ureas were synthesized. All compounds are new and their structures were confirmed by 1H NMR, 13C NMR and mass spectral analyses.
- Zhong, Shi Hua,Fan, Ming Liang,Liu, Bing Yu,Wei, Dong Mei,Liu, Jian Bing
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p. 295 - 300
(2013/07/27)
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- Carboxylic acid-catalyzed one-pot synthesis of cyanoacetylureas and their cyclization to 6-aminouracils in guanidine ionic liquid
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A novel, one-pot, carboxylic acid-catalyzed synthesis of cyanoacetylureas via in situ generated ureas and their cyclization to 6-aminouracils in the presence of the guanidine-based ionic liquid 1,1,3,3-tetramethylguanidine lactate [TMG][Lac] is described. The ureas were synthesized from amines and potassium cyanate, which on reaction with cyanoacetic acid in the presence of acetic anhydride in the same pot afforded cyanoacetylureas, which undergo cyclization in [TMG][Lac] as solvent as well as catalyst to afford 6-aminouracils. One-pot synthesis of cyanoacetylureas, efficient and rapid cyclization, better yield, shorter reaction time, easy workup procedure, and recyclability of the ionic liquid are some advantages of this procedure.
- Chavan, Sunil S.,Shelke, Rupesh U.,Degani, Mariam S.
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p. 399 - 403
(2013/05/21)
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- Poly (ethylene glycol)-bound sulphonic acid as a novel catalyst for synthesis of benzoxazoles
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ABSTRACT Ahighly efficient, simple and rapid method for the preparation of various 2-aminobenzoxazoles and other benzoxazole derivatives using a catalytic amount of poly (ethylene glycol)-bound sulphonic acid (PEG-SO3H) is described. PEG-SO3H is found to be economical and reusable catalyst with low catalytic loading. The percentage yield was found to be satisfactory, experimental set-up and purification of final products is facile and easy. GRAPHICAL ABSTRACT.
- Chikhale, Rupesh V.,Pant, Amit M.,Menghani, Sunil S.,Wadibhasme, Pankaj G.,Khedekar, Pramod B.
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p. 254 - 262
(2013/12/04)
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- Nano cerium oxide as a recyclable catalyst for the synthesis of N-monosubstituted ureas with the aid of acetaldoxime as an effective water surrogate
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A new method for the synthesis of N-monosubstituted ureas has been developed by the reaction of cyanamides with acetaldoxime in the presence of nano cerium oxide as an efficient and recyclable catalyst.
- Sajadi, S. Mohammad,Maham, Mehdi
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p. 623 - 625
(2013/11/06)
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- Synthesis and anticonvulsant evaluation of 2-(substituted benzylidene/ethylidene)-N-(substituted phenyl)hydrazinecarboxamide analogues
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In the present investigation, we described herein the molecular properties prediction by Molinspiration (2008) and synthesized a series of 17 2-(substituted benzylidene/ethylidene)-N-(substituted phenyl) hydrazinecarboxamide analogues. All the title compounds (4a-q) followed the Lipinski "Rule of Five." The synthesized compounds were characterised by elemental analyses and spectral data followed by anticonvulsant activity according to the Antiepileptic Drug Development Programme Protocol. 2-(4-Hydroxybenzylidene)-N-(2-chlorophenyl)hydrazinecarboxamide (4j) was found to be the most active compound of the series showing protection at 4.0 h at a dose of 100 mg/kg against maximal electroshock seizure test and 50 % (2/4, 0.25, 1-2 h) and 100 % (4/4, 0.5 h) protection in 6 Hz psychomotor seizure test without showing any neurotoxicity. N-(2-chlorophenyl)hydrazine carboxamide (3b) showed 100 % (4/4, 0.25-2 h) and 66.6 % (2/3, 4 h) protection in 6 Hz psychomotor seizure test.
- Ahsan, Mohamed Jawed,Khalilullah, Habibullah,Yasmin, Sabina,Jadav, Surender Singh,Stables, James P.,Govindasamy, Jeyabalan
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p. 2746 - 2754
(2013/07/26)
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- Imidazole incorporated semicarbazone derivatives as a new class of anticonvulsants: Design, synthesis and in-vivo screening
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A series of novel imidazole incorporated semicarbazones was synthesized using an appropriate synthetic route and characterized by spectral analysis (IR, 1H NMR, 13C NMR and Mass). The anticonvulsant activity of the synthesized compounds was determined using doses of 30, 100, and 300 mg kg-1 against maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ) induced seizure and minimal neurotoxicity test. Six compounds exhibited protection in both models and 2-(1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene)-N-p- tolylsemicarbazone emerged as the most active compound of the series without any neurotoxicity and significant CNS depressant effect. Liver enzyme estimations (SGOT, SGPT, Alkaline phosphatase) of the compound also showed no significant change in the enzymes levels. Moreover, it caused 80% elevation of γ-amino butyric acid (GABA) levels in the whole mice brain, thus indicating that it could be a promising candidate in designing of a potent anticonvulsant drug.
- Amir, Mohammad,Ali, Israr,Hassan, Mohd. Zaheen
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p. 571 - 580
(2013/07/28)
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- Ionic liquid mediated one-pot synthesis of 6-aminouracils
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A novel, one-pot synthesis of 6-aminouracils via in situ generated ureas and cyanoacetylureas in the presence of an ionic liquid catalyst, 1,1,3,3-tetramethylguanidine acetate, is described. The catalyst can be recycled for five consecutive runs without loss of activity. The mechanism for the ring closure of cyanoacetylurea to 6-aminouracil is also discussed.
- Chavan, Sunil S.,Degani, Mariam S.
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supporting information; experimental part
p. 296 - 299
(2012/03/26)
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- Transamidation of primary amides with amines catalyzed by zirconocene dichloride
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Zirconocene dichloride (Cp2ZrCl2) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80°C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30°C.
- Atkinson, Benjamin N.,Chhatwal, A. Rosie,Lomax, Helen V.,Walton, James W.,Williams, Jonathan M. J.
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supporting information
p. 11626 - 11628,3
(2012/12/12)
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- Transamidation of primary amides with amines catalyzed by zirconocene dichloride
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Zirconocene dichloride (Cp2ZrCl2) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80°C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30°C.
- Atkinson, Benjamin N.,Chhatwal, A. Rosie,Lomax, Helen V.,Walton, James W.,Williams, Jonathan M. J.
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supporting information
p. 11626 - 11628
(2013/01/15)
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- Design, synthesis, and potential CNS activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl- 4H-quinazolin-3-yl)-urea
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Twelve new 1-(4-substituted-phenyl)-3-(4-oxo- 2-methyl-4H-quinazolin-3-yl)- urea were synthesized and screened for anticonvulsant, CNS depressant, and sedativehypnotic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2,3-Disubstitutedquinazolin- 4(3H)-one were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. M3, M4 and M10 were found to be active in both MES screen and scPTZ screen at 0.5 h. All except M11 showed more than 44% decrease in locomotor activity after 1 h of compound administration via actophotometer screen. CNS-depressant activity screened with the help of the forced swim method resulted into some potent compounds. Except for M6 and M11 other tested compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed sedative-hypnotic and CNS depressant activities. Springer Science+Business Media, LLC 2010.
- Kashaw, Sushil K.,Kashaw, Varsha,Mishra, Pradeep,Jain,Stables
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experimental part
p. 738 - 745
(2012/05/20)
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- Oxidation of arylthiourea by cetyltrimethylammonium dichromate
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With a view to investigate the oxidation behaviors of cetyltrimethylammonium dichromate on multifunctional groups, some arylthioureas were subjected to oxidation, both in neutral and in acidic conditions. In neutral conditions, the products were found to be a mixture of corresponding urea and isonitrile. In acidic conditions, the products were corresponding ureas only. A probable mechanism was proposed for the formation of the product, wherein the first step involves coupling of-NH2 and-SH of one molecule to the-NH2 and-SH of another molecule, respectively, which is followed by removal of nitrogen and sulfur. The microwave irradiation resulted in great yield of isonitrile than urea in neutral conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Sahu, Sandhyamayee,Sahoo, Prangya Rani,Patel, Sabita,Mishra
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experimental part
p. 3268 - 3273
(2010/12/24)
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- Oxidation kinetics of arylthioureas by cetyltrimethylammonium dichromate
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Arylthioureas, which are toxic, on oxidation by cetyltrimethylammonium dichromate in acetic acid undergo desulphurization to the corresponding non-toxic arylureas. The mechanism of the oxidation reaction has been studied spectrophotometrically. The rate of reaction is found to be dependent on [CTADC], [phenylthiourea], [acid], [surfactant], polarity of the solvents and reaction temperature. The reaction is fractional order with respect to [substrate] and is catalyzed by acid. With increase in [CTADC], the rate constant decreases. The structure of the substituents has no significant effect on the rate constant. On the basis of various observations, a mechanism has been proposed for the oxidation reaction.
- Sahoo, Prangya Rani,Sahu, Sandhyamayee,Patel, Sabita,Mishra
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scheme or table
p. 1483 - 1487
(2011/02/28)
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- Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction
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Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones (3a-r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,3H)- diones (8a-l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly; beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199.62%) for (M14) Melanoma cells was observed at the tested concentration (10?μM). ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.
- El-Deeb, Ibrahim M.,Bayoumi, Said M.,El-Sherbeny, Magda A.,Abdel-Aziz, Alaa A.-M.
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body text
p. 2516 - 2530
(2010/07/05)
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- Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea
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Several new 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant and sedative-hypnotic activity in the mice. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight synthesized compounds were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. Compounds E1, E6, E9, E12, P3, P4 and P6 were found to be active in the MES screen whereas E1, P4, P6 and P11 were found to be active in the scPTZ screen. All except E6, E11 and P6 showed more than 50% decrease in locomotor activity at 1 h of compound administration via actophotometer screen. CNS depressant activity screened with the help of the forced swim method resulted into some potent compounds. All the compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed promising CNS activities.
- Kashaw, Sushil K.,Kashaw, Varsha,Mishra, Pradeep,Jain,Stables
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experimental part
p. 4335 - 4343
(2009/12/24)
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- Phenylureas. Part 1. Mechanism of the basic hydrolysis of phenylureas
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The mechanism of the hydrolytic decomposition of phenylureas in basic media in the pH range 12 to 14 is investigated. In this pH range a levelling of the rate-pH curve is observed as well as a change of the substituent influence on the hydrolysis rate. These experimental findings suggest the formation of an unreactive side product of the phenylurea in a parasitic side equilibrium at sufficiently high pH. The urea dissociates at the aryl-NH group to give its conjugate base. For the hydrolytic decomposition of phenylureas an addition-elimination mechanism is proposed as has been established for the alkaline hydrolysis of carboxylic acid esters and amides.
- Laudien,Mitzner
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p. 2226 - 2229
(2007/10/03)
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- REACTION OF BENZAMIDE OXIME DERIVATIVES WITH CHLOROCARBONYLSULFENYL CHLORIDE
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Benzamide oxime derivatives (1) were reacted with chlorocarbonylsulfenyl chloride (2) in the presence of a base as a catalyst to afford 3-aryl-4,5-dihydro-1,2,4-thiadiazol-5-one (3), 3-aryl-4,5-dihydro-1,2,4-oxadiazol-5-one (4) and di(benzamide) O,O'-carboxime (5) derivatives in moderate yields.The reaction of N-ethyl-p-toluamide oxime (7) with 2 gave 4-ethyl-4,5-dihydro-3-(p-tolyl)-1,2,4-thiadiazol-5-one (8) and 4-ethyl-4,5-dihydro-3-(p-tolyl)-1,2,4-oxadiazol-5-one (9).
- Kawashima, Etsuko,Ando, Yuko,Takada, Toyozo,Tabei, Katsumi
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p. 181 - 190
(2007/10/02)
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- A kinetic study of the denitrosation and hydrolysis reactions of N-nitrosophenylureas
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The kinetics of the decomposition of N-nitroso-phenylurea in aqueous solution have been studied in the acidity range 0.035-0.36 mol.l-1-HCIO4 and in buffer solutions of pH 3.98-6.14.Below pH 3 the decomposition proceeds mainly by acid catalysed denitrosation, but a small uncatalysed contribution has also been detected.The general acid catalysis, the absence of nucleophilic catalysis by halides and the isotopic effect (kH:kD ca. 1.5) allow a mechanism to be proposed in which the protonation of N-nitrosophenylurea is the rate determining step.The results obtained on studying the denitrosation of some ring-derivatives of N-nitrosophenylurea show a little effect on reaction rate.The mechanism proposed for the hydrolysis reaction (studied at pH > 3.9) involves the formation of a nitrosourea hydrate under steady state conditions, which undergoes an OH(1-) catalysed reaction yielding benzenediazonium ion and an uncatalysed reaction yielding an unidentified product.This latter pathway is virtually negligible at the highest values of pH worked with.
- Casado, Julio,Castro, Albino,Lorenzo, Francisco Manuel,Meijide, Francisco,Mosquera, Manuel
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p. 597 - 601
(2007/10/02)
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- KINETICS AND MECHANISM OF METHANOLYSIS OF BENZOYL DERIVATIVES OF SUBSTITUTED PHENYLUREAS AND PHENYLTHIOUREAS
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The methanolysis rate constants and dissociation constants have been measured of benzoyl derivatives of substituted phenylureas and phenylthioureas.The dissociation constants of the thio derivatives are higher by 1 order of magnitude and the rate constants are higher by 2 orders of magnitude than the respective values of the oxygen analogues.Logarithms of the rate and dissociation constants have been correlated with Hammett ? constant; the ρ constant of the methanolysis of the oxygen derivatives is almost 2 * higher than that of the thio derivatives, which is explained by a change in the rate-limiting step.Methylation of the phenyl nitrogen atom increases the acidity by almost 2 orders of magnitude.This effect is due obviously to steric hindrance to the conjugation with the adjacent carbonyl or thiocarbonyl group.
- Kavalek, Jaromir,El Bahaie, Said,Sterba, Vojeslav
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p. 2103 - 2110
(2007/10/02)
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- Reactions of 2-Hydroxybenzonitrile with Isocyanates
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Triethylamine catalyzes the reaction of 2-hydroxybenzonitrile (1) with arylisocyanates to form the corresponding carbamates 2a-c, as well as the cyclization of the latter compounds to either 4--3-aryl-2H-1,3-benzoxazin-2-ones 4a-c, or 4-arylamino-2H-1,3-benzoxazin-2-ones 7a-c, depending on the reaction temperature.Under analogous conditions, the carbamates obtained from 1 and 2-chloroethyl isocyanate, 3-chloropropyl isocyanate and ethyl isocyanatoacetate undergo a double cyclization yielding imidazo- and pyrimidobenzoxazinones 13a, b, 17.Upon heating in phenyl ether, compounds 7a-c, rearrange to 2-(2-hydroxyphenyl)-4(3H)-quinazolinones 10a-c.
- Petridou-Fischer, J.,Papadopoulos, E. P.
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p. 1159 - 1167
(2007/10/02)
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- Fluorine Containing Bioactive Heterocycles. Part II. Synthesis of Some New Fluorine Containing Arylglyoxals, Their Hydrates and 1,5-Disubstituted Hydantoins
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Eight new fluorine containing arylglyoxals have been synthesized by the oxidation of the active methyl group of fluorinated acetophenones by selenium dioxide in dioxan-water medium.The corresponding hydrates were obtained by dissolving arylglyoxals in minimum amounts of benzene and adding hot water.Seventeen new fluorine containing 1,5-disubstituted hydantoins were subsequently prepared by the condensation of these glyoxals with arylureas in ethanol and characterized by ir, pmr and mass spectral studies.Representative compounds have been screened for their possible anticonvulsant and analgesic activities.None of the compounds show significant analgesic activity.
- Joshi, Krishna C.,Pathak, Vijai N.,Goyal, Mahendra K.
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p. 1651 - 1653
(2007/10/02)
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