- Enzyme-Inspired Lysine-Modified Carbon Quantum Dots Performing Carbonylation Using Urea and a Cascade Reaction for Synthesizing 2-Benzoxazolinone
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Catalysts as the dynamo of chemical reactions along with solvents play paramount roles in organic transformations in long-lasting modes. Thus, developing effective and biobased catalysts in nontoxic solvents is highly in demand. In this report, carbon quantum dots (CQDs) functionalized with-lysine (Lys-CQDs) were generated from entirely nature-derived materials; they were demonstrated to be a promising catalyst for C-N bond formation in choline chloride urea (ChCl/U), a natural deep eutectic solvent (NADES). Among a number of synthesized CQDs, Lys-CQD turned out to be a powerful catalyst in the model reaction with aniline to afford phenyl urea. This type of transformation is important because aniline as a nucleophile has low activity, and urea is a very weak electrophile but an abundant natural source of the carbonyl moiety at the same time. The optimized reaction was performed under a highly desirable condition without using tedious and toxic workup processes at a low temperature (37 °C for aliphatic amines and 60 °C for aniline derivatives), as well as by embracing the broad scope of products in good to high yields even with weak nucleophiles such as aniline. A proposed acid-activated mechanism was suggested for the model reaction that was further confirmed by detecting ammonia as the leaving group. To show further multifunctionality of the catalyst, a cascade catalysis approach was developed for synthesizing 2-benzoxazolinone, which was furnished in a two-step transformation, starting from 2-aminophenol. Using X-ray crystallography, the structure of the final product in the cascade reaction was also determined. The catalyst was characterized using various analytical techniques including SEM, TEM, AFM, XRD, IR spectroscopy, UV-vis spectroscopy, DLS, and fluorescence spectroscopy. Measuring the acid/base sites by back titration, the catalyst was shown to be highly functionalized by the lysine functional group. The size of the catalyst was determined to be in the range of 1-8 nm, having a well-dispersed surface. In all, Lys-modified CQD, as a metal-free catalyst, was synthesized, characterized, and optimized for carbonylation, as well as a cascade reaction, under mild conditions. The whole process including catalyst synthesis and organic transformations is economically competitive and fulfills all requirements toward viability.
- Hasani, Morteza,Kalhor, Hamid R.
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p. 10778 - 10788
(2021/09/08)
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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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- 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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- 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 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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- Design and synthesis of new 2,5-disubstituted-1,3,4-oxadiazole analogues as anticancer agents
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In continuance of our search for new anticancer agents, we report herein the design, synthesis, and anticancer evaluation of oxadiazole analogues. Two series (4a-h and 4i-q) of new oxadiazole analogues were designed based on heterocyclic (1,3,4-oxadiazole
- Agarwal, Mohit,Singh, Vikram,Sharma, Sachin Kumar,Sharma, Piush,Ansari, Md. Yousuf,Jadav, Surender Singh,Yasmin, Sabina,Sreenivasulu, Reddymasu,Hassan, Mohd. Zaheen,Saini, Vipin,Ahsan, Mohamed Jawed
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p. 2289 - 2303
(2016/10/25)
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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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- 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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- 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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- Synthesis of unsymmetrical diarylureas via Pd-catalyzed C-N cross-coupling reactions
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A facile synthesis of unsymmetrical N,N′-diarylureas is described. The utilization of the Pd-catalyzed arylation of ureas enables the synthesis of an array of diarylureas in good to excellent yields from benzylurea via a one-pot arylation-deprotection protocol, followed by a second arylation.
- Breitler, Simon,Oldenhuis, Nathan J.,Fors, Brett P.,Buchwald, Stephen L.
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p. 3262 - 3265
(2011/08/07)
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- Synthesis and pharmacological screening of some novel chalconyl derivatives of substituted phenyl semicarbazide
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In the present study, we have synthesized chalcone and semicarbazide-linked chalonyl derivatives and the titled compounds confirmed by MS, IR, and 1H NMR techniques. The anticonvulsant activity was determined by maximal electroshock (MES) induced seizure method. A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. The results show the importance of hydrogen bonding for activity. In the present study 5e, 5h, 5i, 6e, 6h, and 6i emerged as the most active molecules, showed significant anticonvulsant of activity. Springer Science+Business Media, LLC 2010.
- Singh, Hemendra Pratap,Pandeya,Chauhan,Sharma, Chandra Shekhar
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experimental part
p. 74 - 80
(2012/02/04)
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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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- Antibacterial and antitubercular activities of some diphenyl hydrazones and semicarbazones
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Condensation of phenoxy or 4-bromophenoxy acetic acid hydrazide and substituted aryl semicarbazides with appropriate carbonyl compounds yield corresponding hydrazones and semicarbazones, respectively. The chemical structure of the synthesized compounds has been confirmed by UV, IR and 'H NMR spectral data. All the compounds have been investigated for their antibacterial activity against ten pathogenic strains and antitubercular activity against Mycobacterium tuberculosis H37 Rv. Compound 4f, Acetic acid, phenoxy-,[l-(4-chlorophenyl) ethylidene] hydrazide has been found to exhibit 80% inhibition in the preliminary antitubercular screening (MIC >6.25 |ig/mL).
- Raja,Agarwal,Mahajan,Pandeya,Ananthan
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experimental part
p. 1384 - 1388
(2011/01/13)
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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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- 1-Benzhydryl-3-phenylurea and 1-benzhydryl-3-phenylthiourea derivatives: New templates among the CB1 cannabinoid receptor inverse agonists
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New 1-benzhydryl-3-phenylurea derivatives and their 1-benzhydryl-3- phenylthiourea isosteres were synthesized and evaluated for their human CB 1 and CB2 cannabinoid receptor affinity. These compounds proved to be selective CB1 cannabinoid receptor ligands, acting as inverse agonists in a [35S]-GTPγS assay. The affinity of 3,5,5′-triphenylimidazolidine-2,4-dione and 3,5,5′-triphenyl-2- thioxoimidazolidin-4-one derivatives, possessing the 1-benzhydryl-3-phenylurea and 1-benzhydryl-3-phenylthiourea moiety, respectively, was also evaluated. In conclusion, the 1-benzhydryl-3-phenylurea scaffold seems to be a new interesting template of CB1 cannabinoid receptor inverse agonists.
- Muccioli, Giulio G.,Wouters, Johan,Scriba, Gerhard K. E.,Poppitz, Wolfgang,Poupaert, Jacques H.,Lambert, Didier M.
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p. 7486 - 7490
(2007/10/03)
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