- Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells
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Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamid
- Piven, Yuri A.,Yastrebova, Margarita A.,Khamidullina, Alvina I.,Scherbakov, Alexander M.,Tatarskiy, Victor V.,Rusanova, Julia A.,Baranovsky, Alexander V.,Zinovich, Veronica G.,Khlebnicova, Tatyana S.,Lakhvich, Fedor A.
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supporting information
(2021/11/30)
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- Synthetic Studies toward 1,2,3,3a,4,8b-Hexahydropyrrolo[3,2-b]indole Core. Unusual Fragmentation with 1,2-Aryl Shift
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Base-assisted transformations of 2-(3-oxoindolin-2-yl)acetonitriles were investigated. Unexpectedly, attempted reactions of substrates possessing nonprotected nitrogen atoms were accompanied by unusual extrusions of 2-arylacetonitriles, followed by a 1,2-aryl shift to afford 3-hydroxyindolin-2-ones. On the other hand, the reactions for N-alkyl derivatives of oxoindolines took the expected route by only providing 1,2,3,3a,4,8b-hexahydropyrrolo[3,2-b]indoles.
- Aksenov, Alexander V.,Aksenov, Dmitrii A.,Aksenov, Nicolai A.,Aksenova, Anna A.,Aleksandrova, Elena V.,Nobi, Mezvah A.,Rubin, Michael
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p. 1434 - 1444
(2022/01/27)
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- Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma
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A series of new VEGFR-2 inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against hepatocellular carcinoma (HepG-2 cell line). Compound 29b (IC50 = 4.33 ± 0.2 μg/ml) was found to be the most potent derivative as it has showed to be more active than doxorubicin (IC50 = 4.50 ± 0.2 μg/ml) and 78% of sorafenib activity (IC50 = 3.40 ± 0.25 μg/ml). The inhibitory profiles against VEGFR-2 were also assessed for the most promising candidates (16b, 20c, 22b, 24a, 24b, 28c, 28e, 29a, 29b and 29c). Compounds 29b, 29c and 29a exhibited potent inhibitory activities towards VEGFR-2 at IC50 values of 3.1 ± 0.04, 3.4 ± 0.05 and 3.7 ± 0.06 μM, respectively, comparing sorafenib (IC50 = 2.4 ± 0.05 μM). Furthermorer, compound 29b induced apoptosis and arrested the cell cycle growth at G2/M phase. Additionally, in vivo antitumor experiments revealed that compounds 29b and 29c have significant tumor growth inhibition. The test of immuno-histochemical expression of activated caspase-3 revealed that there is a time-dependent increase in cleaved caspase-3 protein expression upon exposure of HepG-2 cells to compound 29b. Moreover, the fibroblastic proliferative index test revealed that compound 29b could attenuate liver fibrosis. Docking studies also supported the results concluded from the biological screening via prediction of the possible binding interactions of the target compounds with VEGFR-2 active sites using the crystal structure of VEGFR-2 downloaded from the Protein Data Bank, (PDB ID: 2OH4) using Discovery Studio 2.5 software. Further structural optimization of the most active candidates may serve as a useful strategy for getting new lead compounds in search for powerful and selective antineoplastic agents.
- Eissa, Ibrahim.H.,Ibrahim, Mohammed K.,Metwaly, Ahmed M.,Belal, Amany,Mehany, Ahmed B.M.,Abdelhady, Alsayed A.,Elhendawy, Mostafa A.,Radwan, Mohamed M.,ElSohly, Mahmoud A.,Mahdy, Hazem A.
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- Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers
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Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Accordingly, new quinazoline-based derivatives having the structural features of VEGFR-2 inhibitors were designed and synthesized. Anti-proliferative activities were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Compounds 26b, 29a, 29b and 30 showed excellent anti-cancer activities against all cell lines. Moreover, compound 31 was the most active with IC 50 values of 3.97 ± 0.2, 4.83 ± 0.2 and 4.58 ± 0.3 μM, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities, compound 31 showed a high activity against VEGFR-2 with an IC50 value of 2.5 ± 0.04 μM, almost equal to that of sorafenib (IC50 = 2.4 ± 0.05 μM). Further studies revealed the ability of this promising quinazoline derivative 31 to induce apoptosis and arrest cell cycle growth at G2/M phase. In vivo antitumor activities of the synthesized compounds revealed that compounds 30 and 31 possessed significant tumor growth inhibition effect. Molecular docking studies were also performed and finally we can say that VEGFR-2 inhibition confers the reported cytotoxic activities.
- Belal, Amany,Eissa, Ibrahim H.,El-Gamal, Kamal M. A.,El-Sharkawy, Abdou,Elhendawy, Mostafa A.,Elsohly, Mahmoud A.,Ibrahim, Mohammed K.,Mahdy, Hazem A.,Mehany, Ahmed B. M.,Metwaly, Ahmed M.,Radwan, Mohamed M.
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- A straightforward TBHP-mediated synthesis of 2-amidobenzoic acids from 2-arylindoles and their antimicrobial activity
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A simple and highly efficient strategy has been developed for the synthesis of 2-amidobenzoic acids through the tert-butyl hydroperoxide (TBHP)-mediated oxygenation and sequential ring opening of 2-arylindoles in a one-pot fashion under metal-free aerobic conditions. The developed synthetic protocol is operationally simple, tolerates a wide range of functional groups, and is amenable to the gram-scale. Radical trapping experiments revealed that the reaction involves a radical pathway. The synthesized compounds (2a-s) were tested for in vitro antimicrobial activity. Among all screened compounds, 2d showed the maximum antibacterial activity against P. aerugunosa (ZOI = 17 mm, MIC = 32 μg mL-1) and compounds 2d and 2p showed the maximum (32 μg mL-1) antifungal activity against A. flavus and C. albicans.
- Patel, Om P.S.,Dhiman, Shiv,Khan, Shahid,Shinde, Vikki N.,Jaspal, Sonam,Srivathsa, Manu R.,Jha, Prabhat N.,Kumar, Anil
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p. 5962 - 5970
(2019/06/24)
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- Palladium catalyzed chemo- and site-selective C-H acetoxylation and hydroxylation of oxobenzoxazine derivatives
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An efficient protocol for the introduction of acetoxy and hydroxy functionalities on unactivated aryl sp2 carbons of oxobenzoxazine derivatives via an ortho-C-H activation reaction using a palladium catalyst has been developed for the first tim
- Bakthadoss, Manickam,Vijay Kumar, Polu,Kumar, Ravan,Agarwal, Vishal
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supporting information
p. 4465 - 4469
(2019/05/16)
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- A new series of Schiff base derivatives bearing 1,2,3-triazole: Design, synthesis, molecular docking, and α-glucosidase inhibition
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A series of new Schiff bases bearing 1,2,3-triazole 12a?o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug aca
- Nasli-Esfahani, Ensieh,Mohammadi-Khanaposhtani, Maryam,Rezaei, Sepideh,Sarrafi, Yaghoub,Sharafi, Zeinab,Samadi, Nasser,Faramarzi, Mohammad Ali,Bandarian, Fatemeh,Hamedifar, Haleh,Larijani, Bagher,Hajimiri, Mirhamed,Mahdavi, Mohammad
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- Radical-Induced, Palladium-Catalyzed C–H Activation: An Approach to Functionalize 4H-Benzo[d][1,3]oxazin-4-one Derivatives by Using Toluenes, Aldehydes, and Benzyl Alcohols
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Toluenes, aldehydes, and benzyl alcohols have been utilized in the radical-induced direct functionalization of 4H-benzo[d][1,3]oxazin-4-one derivatives by using a palladium-catalyzed C–H activation strategy. The stability, low toxicity, and ease of access
- Kumar, Prashant,Gupta, Mohit,Bahadur, Vijay,Parmar, Virinder S.,Singh, Brajendra K.
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supporting information
p. 1552 - 1558
(2018/04/20)
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- Latent Bronsted Base Solvent-Assisted Amide Formation from Amines and Acid Chlorides
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Weakly basic amines, including even neutral amines such as nitroaniline and aminocarboxylic acids, react with acid chlorides very efficiently in N, N -dimethylacetamide (DMAC), without addition of a base, to give the corresponding amides in high yields. The role of DMAC and related solvents as latent Bronsted bases was studied in these amidation reactions. Less basic amines, such as aromatic amines, reacted with benzoyl chloride faster than more basic aliphatic amines.
- Otsuka, Rikuto,Maruhashi, Kazuo,Ohwada, Tomohiko
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supporting information
p. 2041 - 2057
(2018/05/04)
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- Aminobenzoic acid derivatives as antioxidants and cholinesterase inhibitors; synthesis, biological evaluation and molecular docking studies
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Cholinesterase namely, acetyl- and butyrylcholinesterase (AChE and BChE, respectively), has been recognized as a primary class of enzyme that hydrolyzes the acetylcholine (ACh) neurotransmitter in synaptic junctions. Diminished levels of the neurotransmitter in synaptic junction lead to Alzheimerís disease (AD). Inhibition of cholinesterase is thus, an attractive strategy for AD treatment. The study includes the synthesis and characterization of a series of 2-, 3- and 4-aminobenzoic acid derivatives (1a?5c), their biological screening against cholinesterase enzyme and molecular docking study to demonstrate putative binding modes. Antioxidant potential of the synthesized series was also determined. The cholinesterase enzyme inhibition assay showed that compound 5b has the highest inhibition potential against acetylcholinesterase with an IC50 value of 1.66 ± 0.03 μM while in case of butyrylcholinesterase, compound 2c has the highest inhibitory potential with an IC50 value of 2.67 ± 0.05 μM. Molecular docking studies supports the results of enzyme inhibition potential with binding energy value ?G = -9.54 Kcal mol-1 for compound 5b in case for acetylcholinesterase while for butyrylcholinesterase, ?G = -5.53 Kcal mol-1 was obtained for compound 2c. The synthesized series of compounds also shows mild to moderate antioxidant potential. The benzoyl- containing compounds shows better antioxidant activity as compared to other derivatives of the synthesized series. Based on the molecular docking studies and enzyme inhibition potential, the synthesized series of compounds can be regarded as potent cholinesterase inhibitors and can be used for designing and synthesizing more potent drugs for Alzheimerís disease and neurodegenerative diseases.
- Iftikhar, Kiran,Murtaza, Shahzad,Kousar, Naghmana,Abbas, Aadil,Tahir, Muhammad Nawaz
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p. 385 - 396
(2018/04/23)
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- Recyclable keggin heteropolyacids as an environmentally benign catalyst for the synthesis of new 2-benzoylamino-n-phenyl-benzamide derivatives under microwave irradiations at solvent-free conditions and the evaluation of biological activity
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2-Benzoylamino-N-phenyl-benzamide derivatives (5a–h) were prepared from 2-phenyl-3,1-(4H)-benzoxazin-4-one 3 and substituted anilines 4a–h in the presence of a Keggin-type heteropolyacids series (H3PW12O40·13H2O
- Ighilahriz-Boubchir, Karima,Boutemeur-Kheddis, Baya,Rabia, Cherifa,Makhloufi-Chebli, Malika,Hamdi, Maamar,Silva, Artur M. S.
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- Silver-Mediated Synthesis of 4H-Benzoxazin-4-ones by Intramolecular Decarboxylative O-Acylation Reactions with α-Oxocarboxylic Acid
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The first example of an intramolecular decarboxylative acylation reaction for the synthesis of 4H-benzoxazin-4-one derivatives has been described. The silver-mediated reaction has a broad substrate scope and provides a mild and rapid approach to the corre
- Bharathimohan, Kuppusamy,Ponpandian, Thanasekaran,Jafar, Ahamed A.
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p. 2806 - 2813
(2017/05/29)
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- One-pot synthesis of polyhydropyrido[1,2-a]indoles and tetracyclic quinazolinones from 2-arylindoles using copper-mediated oxidative tandem reactions
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We developed facile one-pot methods for the transformation of 2-arylindoles to polyhydropyrido[1,2-a]indoles and tetracyclic quinazolinones. The copper-catalyzed oxidation of 2-arylindoles to C-acylimines followed by aza-Diels–Alder reactions or oxidative
- Yamashita, Mitsuaki,Nishizono, Yukari,Himekawa, Seiya,Iida, Akira
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p. 4123 - 4131
(2016/07/06)
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- Silver- versus gold-catalyzed sequential oxidative cyclization of unprotected 2-alkynylanilines with oxone
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Unprecedented domino oxidative cyclization reactions of unprotected 2-alkynylanilines to give functionalized 4H-benzo[d][1,3]oxazin-4-one or benzisoxazole derivatives in moderate to good yields are achieved by silver vs. gold selective catalysis. The search for the optimal reaction conditions revealed the divergent catalytic activity of NaAuCl4·H2O and AgNO3.
- Arcadi,Chiarini,Vecchio, L. Del,Marinelli,Michelet
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supporting information
p. 1458 - 1461
(2016/01/25)
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- Palladium-catalyzed C-H bond carboxylation of acetanilides: An efficient usage of N,N-dimethyloxamic acid as the carboxylate source
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N,N-Dimethyloxamic acid can be successfully employed as a carboxylate precursor in the palladium-catalyzed direct C-H carboxylation of acetanilides. The reaction proceeds smoothly under mild conditions over a broad range of substrates with high functional group tolerance, affording substituted N-acyl anthranilic acids in moderate to high yields.
- Wu, Yinuo,Jiang, Cheng,Wu, Deyan,Gu, Qiong,Luo, Zhang-Yi,Luo, Hai-Bin
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supporting information
p. 1286 - 1289
(2016/01/15)
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- COMPOUND HAVING ZNF143 INHIBITORY ACTIVITY AND USE THEREOF
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PROBLEM TO BE SOLVED: To provide a compound having a ZNF143 inhibitory activity as well as to provide a ZNF143 inhibitory agent and pharmaceutical composition containing the same. SOLUTION: Provided is a compound represented by formula (I) or a salt thereof as well as a ZNF143 inhibitory agent containing the same and a pharmaceutical composition having the same as an active ingredient. A-B-C-D (I)[A is H, a methyl group, a naphthyl group, a phenyl group or a nitrogen-containing heterocyclic ring; B is as shown below, and C is an amide bond or a heteroaromatic ring containing N and O; D is a substituted/unsubstituted phenyl group or a monocyclic heteroaromatic ring containing N or S; and C and D are both fused heterocyclic ring or the like optionally having a substituent group.]. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0339
(2016/10/27)
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- Synthetic studies and antibacterial activity of nucleobases and their N- and S-glucosides from 2-amino benzoic acid and its benzamido derivatives
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A series of S-glucosides 11a-14a and their benzamido derivatives 11b-14b have been synthesized by reacting D-glucose with thiol groups of 5-(2′-aminophenylene)-1,3,4-oxadiazole-2-thioles 7(a,b), 5-(2′-aminophenylene)-1,3,4-thiadiazole-2-thiols 8(a,b), 5-(2′-aminophenylene)-1,2,4-triazole-3-thiols 9(a,b) and 5-(2′-aminophenylene)-4-N-amino-1,2,4-triazole-3-thiols 10(a,b). The thiols 7(a,b)-10(a,b) have been synthesized from hydrazides 3(a,b) which already been synthesized from 2-aminobenzoic acid and its benzamido derivative. All synthesized compounds were characterized by IR, UV,1H- and13C- NMR. Nucleobases and a representative of S-glycoside were tested in vitro against the following microorganisms: two Gram-positive bacteria Staphylococcus aureus and Bacillus cereusand two Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and they exhibited significant effects. Amykacine was used as positive standard.
- Benhammadi, Samia,Iraten, Salima,Othman, Adil A.
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p. 2567 - 2576
(2016/11/22)
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- Design, synthesis and in vivo screening of some novel quinazoline analogs as anti-hyperlipidemic and hypoglycemic agents
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A novel series of substituted quinazoline derivatives were designed, synthesized and evaluated for their hypolipidemic activity in cholesterol induced hyperlipidemic rats. In vivo screening concluded that compounds A-4, C-5 and C-6 have shown potent antihyperlipidemic activity by decreasing the plasma level of triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), followed by increase in level of high density lipoprotein (HDL).
- Mokale, Santosh N.,Palkar, Akash D.,Dube, Pritam N.,Sakle, Nikhil S.,Miniyar, Pankaj B.
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supporting information
p. 272 - 276
(2016/01/09)
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- Precursor-directed combinatorial biosynthesis of cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates in saccharomyces cerevisiae
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Biological synthesis of pharmaceuticals and biochemicals offers an environmentally friendly alternative to conventional chemical synthesis. These alternative methods require the design of metabolic pathways and the identification of enzymes exhibiting ade
- Eudes, Aymerick,Benites, Veronica Teixeira,Wang, George,Baidoo, Edward E.K.,Lee, Taek Soon,Keasling, Jay D.,Loqué, Dominique
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- Benzenesulfonamides incorporating bulky aromatic/heterocyclic tails with potent carbonic anhydrase inhibitory activity
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Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl- or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with KIs of 7.6-322 nM against hCA I, of 0.06-85.4 nM against hCA II; of 6.7-152 nM against hCA IX and of 0.49-237 nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail.
- Bozdag, Murat,Alafeefy, Ahmed M.,Vullo, Daniela,Carta, Fabrizio,Dedeoglu, Nurcan,Al-Tamimi, Abdul-Malek S.,Al-Jaber, Nabila A.,Scozzafava, Andrea,Supuran, Claudiu T.
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p. 7751 - 7764
(2015/12/20)
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- One-pot approach to 2-arylbenzoxazinone derivatives from 2-alkynylanilines using copper-mediated tandem reactions
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In this study, we describe a one-pot method to obtain a variety of 2-arylbenzoxazinones and N-benzoyl anthranilic acid by using a copper catalyst and molecular oxygen as oxidants. This protocol involves tandem cyclization and oxidative processes of 2-alkynylanilines to afford significant motifs in synthetic and medicinal chemistry with moderate yields. We also demonstrated that combining the Sonogashira coupling and the developed method realized the synthesis of 2-arylbenzoxazinones derivatives from commercially available 2-iodoanilines and terminal acetylenes.
- Yamashita, Mitsuaki,Iida, Akira
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p. 5746 - 5751
(2015/03/30)
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- Copper-mediated oxidative tandem reactions with molecular oxygen: Synthesis of 2-arylbenzoxazinone derivatives from indoles
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We developed an efficient method for the transformation of indoles by utilizing a copper catalyst and molecular oxygen as the oxidant. The transformation involves a tandem oxidative process of 2-arylindoles. Our reaction afforded a variety of N-benzoyl an
- Yamashita, Mitsuaki,Iida, Akira
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p. 2991 - 2993
(2014/05/06)
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- Design and synthesis of quinazolinone tagged acridones as cytotoxic agents and their effects on EGFR tyrosine kinase
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In a quest for finding potent cytotoxic molecules, we have designed and synthesized a new scaffold by tagging quinazolinones with an acridone moiety. The new acridone-4-carboximide derivatives were evaluated for their cytotoxic potentials against the MCF7 breast cancer cell line and three colon cancer cell lines (LS174T, SW1398, and WiDr). Compound 26 showed relatively potent cytotoxic activity among the derivatives, against all the cell lines tested. Mechanistic studies for the selected derivatives 7, 8, 16, 17, 25, and 26 were conducted through in vitro EGFR tyrosine kinase inhibition studies. The results indicate that compound 26 has a better EGFR tyrosine kinase inhibitory profile. The in vitro EGFR inhibition data was correlated with the cytotoxic properties, and molecular docking studies were performed with regard to the receptor autophosphorylation sites of the protein kinase domain of the EGFR.
- Babu, Yarlagadda Rajesh,Bhagavanraju, Mantripragada,Reddy, Gade Deepak,Peters, Godefridus J.,Prasad, Velivela V. S. Rajendra
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p. 624 - 634
(2014/11/08)
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- Synthesis and characterization of quinazoline derivatives: Search for hybrid molecule as diuretic and antihypertensive agents
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To explore the pharmacological and structure-activity relationship of a series of N-substituted-(4-oxo-2-substituted-phenylquinazolin-3-(4H)-yl), substituted benzene sulfonamide derivatives (1-25) were synthesized from substituted anthranilic acids derive
- Rahman, Mujeeb Ur,Rathore, Ankita,Siddiqui, Anees A.,Parveen, Gazala,Yar, M. Shahar
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p. 733 - 743
(2014/12/11)
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- Discovery of novel bacterial RNA polymerase inhibitors: Pharmacophore-based virtual screening and hit optimization
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The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between σ70 and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies compared to clinically used rifampicin.
- Hinsberger, Stefan,Hüsecken, Kristina,Groh, Matthias,Negri, Matthias,Haupenthal, J?rg,Hartmann, Rolf W.
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p. 8332 - 8338
(2013/12/04)
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- Synthesis of some new glutamine linked 2,3-disubstituted quinazolinone derivatives as potent antimicrobial and antioxidant agents
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A series of novel glutamine linked 2,3-disubstituted quinazolinone conjugates was synthesized from methyl anthranilate and different substituted acids and acid chlorides. The compounds 5a-l were prepared in good yields. All compounds were screened for their antibacterial activity against Gram-positive and Gram-negative bacteria and for antifungal activity against Candida albicans and Aspergillus flavus using paper disk diffusion technique. The minimum inhibitory concentrations of the compounds were also determined by agar streak dilution method. The compound 5b was found to exhibit the most potent in vitro anti-microbial activity. When tested for their antioxidant activity, compounds 5i and 5l showed potent radical scavenging activity, while compound 5g had moderate effect against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, nitric oxide, and superoxide radical scavenging assays. These results suggest that, the three quinazolinone analogs (5g, 5i, and 5l) could be considered as useful templates for future development to obtain more potent antioxidant agents.
- Prashanth,Revanasiddappa
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p. 2665 - 2676
(2013/07/26)
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- Kinetics and mechanism of the base-catalyzed oxygenation of 1H-2-phenyl-3-hydroxy-4-oxoquinolines in DMSO/H2O
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The oxygenation of 4′-substituted 1H-2-phenyl-3-hydroxy-4- oxoquinolines (PhquinH2) in a DMSO/H2O (50/50) solution leads to the cleavage products at the C2-C3 bond in about 75% yield at room temperature. The oxygenation, deduced from the product compositions, has two main pathways, one proceeding via an endoperoxide leading to CO-release, and the other through a 1,2-dioxetane intermediate without CO-loss. The reaction is specific base-catalyzed and the kinetic measurements resulted in the rate law -a...?[PhquinH2]/a...?t=kOH - [OH-] [PhquinH2] [O2]. The rate constant, activation enthalpy, and entropy at 303.16 K are as follows: kOH-=(2.42±0.03)×103mol -2L2s-1; ΔG?=73. 13±4.02 kJ mol-1; ΔH?=70.60±4. 04 kJ mol-1; ΔS?=-28±2 J mol -1 K-1. The reaction fits a Hammett linear free energy relationship for 4′-substituted substrates, and electron-releasing groups make the oxygenation reaction faster (ρ=-0.258). The EPR spectrum of the reaction mixtures showed the presence of the organic radical 1H-2-phenyl-3-oxyl-4-oxoquinoline and superoxide ion due to single electron transfer from the carbanion to dioxygen. The pathway via 1,2-dioxetane could be proved by chemiluminescence measurements.
- Czaun, Miklós,Speier, Gábor,Kaizer, József,El Bakkali-Taheri, Nadia,Farkas, Etelka
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p. 6666 - 6672
(2013/07/26)
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- Substituent effects on energetics of peptide-carboxylate hydrogen bonds as studied by 1H NMR spectroscopy: Implications for enzyme catalysis
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Substituent effects in N-H···O hydrogen bonds were estimated by comparing the acidities of two series of model compounds: N-benzoylanthranilic acids (A) and 4-benzoylamidobenzoic acids (B). Intramolecular N-H···O hydrogen bonds were found to be present in the A series of compounds, while B acids were used as control models. The respective pKa values for A and B acids were determined experimentally in DMSO solution using proton NMR spectroscopy. With X = H, the pKa for A and B acids were observed to be 7.6 and 11.6, respectively, a difference of 4.0 units (ΔpKa). However, with X = p-NO 2, the ΔpKa value between A and B acids increased to 4.7 units: the pKa values for A and B acids were determined as 6.7 and 11.4, respectively. The ΔpKa values between A and B acids as a function of the X substituents were studied in 10 other examples. The effects of X substituents in A acids could be predicted on the basis of the observed linear Hammett correlations, and the sensitivity of each substituent effect was found to be comparable to those observed for the ionization of substituted benzoic acids (ρ = 1.04 for A acids, and ρ = 1.00 for benzoic acids).
- Emenike, Bright U.,Liu, Albert Tianxiang,Naveo, Elsy P.,Roberts, John D.
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p. 11765 - 11771
(2014/01/06)
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- Bio-inspired flavonol and quinolone dioxygenation by a non-heme iron catalyst modeling the action of flavonol and 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases
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The mononuclear complex, FeIII(O-bs)(salen) (salenH2 = 1,6-bis(2-hydroxyphenyl)-2,5-diaza-hexa-1,5-diene; O-bsH = O-benzoylsalicylic acid) was synthesized as synthetic enzyme-depside complex, and characterized by spectroscopic methods and X-ray crystal analysis. The dioxygenation of flavonol (flaH) and 3-hydroxy-4-quinolone (quinH2) derivatives in the presence of catalytic amounts of FeIII(O-bs)(salen) results in the oxidative cleavage of the heterocyclic ring to give the corresponding O-benzoylsalicylic and anthranilic acid derivatives with concomitant release of carbon monoxide. These reactions can be regarded as biomimetic functional models with relevance to the iron-containing flavonol and the cofactor-independent 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases.
- Pap, József S.,Matuz, Andrea,Baráth, Gábor,Kripli, Balázs,Giorgi, Michel,Speier, Gábor,Kaizer, József
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experimental part
p. 15 - 21
(2012/06/15)
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- Synthesis and biological activities of some fused benzopyrimidine-4-ones
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Condensation of anthranilic acid with acid chloride afforded 2-substituted benzoic acids which on cyclization with different primary amines yielded the corresponding 2,3-disubstituted quinazolin-4-(3H)-ones (B1-B 6). The structure of
- Vachala, Seekarajapuram Dinakaran,Srinivasan, Keloth Kaitheri
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p. 189 - 192
(2013/09/24)
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- Design and synthesis of some novel 3-[5-(4-substituted) phenyl- 1,3,4-oxadiazole-2yl]-2-phenylquinazoline-4(3H)-ones as possible anticonvulsant agent
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A novel series 7(a-f) 3-[5-(4-substituted) phenyl- 1,3,4-oxadiazole-2yl]-2 phenylquinazoline-4(3H)-ones have been synthesized and screened for its anticonvulsant and neurotoxic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2,3-disubstitutedquinazolin- 4(3H)-ones were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data were consistent with the structure of newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. In the prepared series, 7a was found to be active in the MES screen at 0.5 h, whereas 7f showed anticonvulsant activity at both 0.5 and 4 h. Springer Science+Business Media, LLC 2010.
- Gupta, Anjali,Kashaw, Sushil K.,Jain, Neha,Rajak, Harish,Soni, Abhishek,Stables
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experimental part
p. 1638 - 1642
(2012/06/05)
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- Synthetic applications of Pd(II)-catalyzed C-H carboxylation and mechanistic insights: Expedient routes to anthranilic acids, oxazolinones, and quinazolinones
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A Pd(II)-catalyzed reaction protocol for the carboxylation of ortho-C-H bonds in anilides to form N-acyl anthranilic acids has been developed. This reaction procedure provides a novel and efficient strategy for the rapid assembly of biologically and pharmaceutically significant molecules, such as benzoxazinones and quinazolinones, from simple anilides without installing and removing an external directing group. The reaction conditions are also amenable to the carboxylation of N-phenyl pyrrolidinones. A monomeric palladacycle containing p-toluenesulfonate as an anionic ligand has been characterized by X-ray crystallography, and the crucial role of p-toluenesulfonic acid in the activation of C-H bonds in the presence of carbon monoxide is discussed. Identification of two key intermediates, a mixed anhydride and benzoxazinone formed by reductive elimination from organometallic Ar(CO)Pd(II)-OTs species, provides mechanistic evidence for a dual-reaction pathway.
- Giri, Ramesh,Lam, Jonathan K.,Yu, Jin-Quan
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supporting information; experimental part
p. 686 - 693
(2010/03/25)
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- Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives
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Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared and screened for their analgesic, anti-inflammatory activity and acute toxicity. Four compounds were more potent analgesic agents than the reference drug Indomethacin and thirteen compounds showed significant anti-inflammatory activity. Seven compounds showed combined ability to inhibit both pain and inflammation. Compounds tested for acute toxicity showed no toxic symptoms or mortality rates 24 h post-administration implying their good safety margin.
- Alafeefy, Ahmed M.,Kadi, Adnan A.,Al-Deeb, Omar A.,El-Tahir, Kamal E.H.,Al-Jaber, Nabila A.
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scheme or table
p. 4947 - 4952
(2010/11/20)
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- Brine-mediated efficient benzoylation of primary amines and amino acids
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Benzoylation of primary amines and amino acids is efficiently carried out in a brine solution using a stoichiometric amount of benzoyl chloride followed by trituration with aqueous saturated bicarbonate solution. Copyright Taylor & Francis Group, LLC.
- Chattopadhyay, Gautam,Chakraborty, Suchandra,Saha, Chandan
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experimental part
p. 4068 - 4075
(2009/04/11)
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- Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: New lead compounds for the development of anticancer agents
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Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin, flufenamic acid, and related compounds have been recently identified as potent inhibitors of AKR1C3. We report that some other NSAIDs (diclofenac and naproxen) also inhibit AKR1C3, with the IC50 values in the low micromolar range. In order to obtain more information about the structure-activity relationship and to identify new leads, a series of compounds designed on the basis of NSAIDs were synthesized and screened on AKR1C3. The most active compounds were 2-[(2,2-diphenylacetyl)amino]benzoic acid 4 (IC50 = 11 μM) and 3-phenoxybenzoic acid 10 (IC50 = 0.68 μM). These compounds represent promising starting points for the development of new anticancer agents.
- Gobec, Stanislav,Brozic, Petra,Rizner, Tea Lanisnik
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p. 5170 - 5175
(2007/10/03)
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- A new synthesis of 2-substituted 4H-3,1-benzoxazin-4-ones by cyanuric chloride cyclodehydration of N-benzoyl- and N-acylanthranilic acids
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A new and a convenient method for the synthesis of aryl- and alkyl-2-substituted 4H-3,1-benzoxazin-4-ones by cyclodehydration of N-benzoyl- and N-acylanthranilic acid by cyanuric chloride is described.
- Khajavi, Mohammad S.,Shariat, Seyed M.
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p. 1159 - 1165
(2007/10/03)
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- 3,6-Dibenzoxyl-1,2-pyridazine: A new versatile benzoyl transferring agent for NH2, -OH and -SH benzoylations
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A newly synthesized 3,6-dibenzoxyl-1,2-pyridazine 3 has been investigated for its potential to transfer the benzoyl group to various organic substrates carrying -NH2, -OH and -SH groups. The benzoyl transfer is fairly general in scope, occurs under convenient conditions and provides good to excellent yields of benzoylated products. Moreover, by choosing proper conditions, it is possible to achieve chemoselective benzoylation in bi-functional molecules. For instance, N-benzoylation of aromatic amines can be selectively accomplished over that of aliphatic amines and vice versa by manipulating reaction conditions. Selective N- or O-benzoylation in aminophenols is also possible. Although, not studied in detail, we final that dibenzoate 3 can also be used to effect C-benzoylation of reactive phenols and ketones, as exemplified by the C-benzoylation of resorcinol and acetophenone, respectively. Dibenzoate 3, besides being a crystalline, easy to handle, solid possesses twice the potential as an acyl carrier compared to the other known acyl carriers. These features make 3 as an attractive choice for many applications pertaining to benzoyl transfer reactions.
- Mashraqui, Sabir Hussain,Shivaji, Jadhav Latika
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p. 927 - 935
(2007/10/03)
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- Synthesis and biological properties of selected 2-aryl-4(3H)-quinazolinones
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A series of 2-aryl-4(3H)quinazolinones were prepared as parent systems of rutaecarpine and luoitonin A and their biological properties (cytotoxicity and COX-2 inhibitory activity) were evaluated.
- Lee, Eung Seok,Son, Jong Keun,Na, Young Hwa,Jahng, Yurngdong
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p. 325 - 330
(2007/10/03)
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- The design and synthesis of novel orally active inhibitors of AP-1 and NF-κB mediated transcriptional activation. SAR of in vitro and in vivo studies
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We have developed novel orally active quinazoline analogues as inhibitors of AP-1 and NF-κB mediated transcriptional activation. Among the derivatives prepared, 1-[2-(2-thienyl)quinazolin-4-ylamino]-3-methyl-3- pyrroline-2,5-dione (10) showed significant activity in an adjuvant-induced arthritis rat model by reducing the swelling by 65% in the non-injected foot. The synthesis, structure-activity relationship, and in vivo activity are described.
- Palanki, Moorthy S. S.,Erdman, Paul E.,Ren, Minghuan,Suto, Mark,Bennett, Brydon L.,Manning, Anthony,Ransone, Lynn,Spooner, Cheryl,Desai, Sonal,Ow, Arnie,Totsuka, Ryuichi,Tsao, Peter,Toriumi, Wataru
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p. 4077 - 4080
(2007/10/03)
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- 2-Acylpyridazin-3-ones: Novel mild and chemoselective acylating agents for amines
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2-Acyl-4,5-dichloropyridazin-3-ones served as excellent novel N-acylating reagents for amines under neutral conditions in organic solvent. They are convenient, chemoselective and easy to handle stable N-acylating reagents of amines.
- Kang, Young-Jin,Chung, Hyun-A,Kim, Jeum-Jong,Yoon, Yong-Jin
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p. 733 - 738
(2007/10/03)
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- The base-catalyzed oxygenation of quinoline derivatives
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The base-catalyzed oxygenation of 1H-2-phenyl-3-hydroxy-4-oxoquinoline leads to cleavage products derived from either an endoperoxide or a 1,2-dioxetan intermediate. A persistent 1H-2-phenyl-3-oxy-4-oxoquinoline radical could also be detected by EPR in the reaction mixture.
- Czaun, Miklós,Speier, Gábor
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p. 5961 - 5963
(2007/10/03)
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- Production of 3-Benzoyl-2,1-benzisoxazoles, 2-Phenyl-4H-3,1-benzoxazin-4-ones, and Novel Quinolinone Derivatives from 2-Phenylquinolin-4(1H)-ones and Sodium Dichloroisocyanurate
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A simple synthesis of certain 3-benzoyl-2,1-benzisoxazoles 6 is accomplished via treatment of the corresponding 2-phenylquinolin-4(1H)-one 1 with sodium dichloroisocyanurate 2 in methanolic aq. alkali; the isomeric 2-phenyl-4H-3,1-benzoxazin-4-one 7 is al
- Staskun, Benjamin,Es, Theodorus van
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p. 511 - 516
(2007/10/02)
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- A STUDY OF THE MECHANISM OF HYDROLYSIS OF SINGLE CRYSTALS OF 2-PHENYL-4H-3,1-BENZOXAZIN-4-ONE
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Single crystals of 2-phenyl-4H-3,1-benzoxazin-4-one, 1, (a = 13.315 Angstroem, b = 3.912 Angstroem, c = 20.465 Angstroem, β = 94.93 deg, Z = 4, P21/n, R = 0.047) have been found to undergo hydrolysis at room temperature.Reacting single crystals
- Etter, M. C.,Lipkowska, Z. U.,Decoret, C.,Royer, J.,Bayard, F.,Vicens, J.
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- Studies on Potential Antibacterial and Chelating Agents: Part III - Synthesis, Characterization and Biological Activity of Co(II), Ni(II) and Cu(II) Chelates with Some Sulphonamido and Benzamido Derivatives of Aminobenzoic Acids
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The complexing behaviour of some amidobenzoic acids towards Co(II), Ni(II) and Cu(II) has been studied.Eleven complexes of the type M(RH)2 where RH2 = o, m and p-benzenesulphonamidobenzoic acids, o-(p-toluenesulphonamido)benzoic acid and o-benzamidobenzoi
- Nandi, M. M.,Debnath, P.
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p. 498 - 501
(2007/10/02)
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- Structure and Solid Hydrolysis of 3,1-Benzoxazin-4-ones
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Solid hydrolysis of 2-substituted 3,1-benzoxazin-4-ones are presented.O18 experiments with labelled water and hydrolysis in acidic comditions show the reaction occurs on >C=N- function.A protonated intermediate for the reaction is proposed.Theoretical calculations are in agreement with the assumed intermediate.
- Vicens, Jacques,Decoret, Claude,Gaget, Christine,Etter, Margaret C.,Errede, Lou A.
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- SOLID STATE HYDROLYSIS OF ACETYLANTHRANYL - ASSISTANCE BY HYDROGEN BONDING
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18O and acidic hydrolysis in the solid state of acyl anthranyls are presented.The role of H-bonds in assisting the reactions is discussed.
- Vicens, J.,Etter, M. C.,Errede, L. A.
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p. 723 - 724
(2007/10/02)
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- Reactions of 2-Isocyanatobenzoyl Chlorides with Phenylmagnesium Bromide: Synthesis of 2-Phenyl-3,1-benzoxazin-4(H)-ones, N-Benzoyl-2-aminobenzophenones, α-(2-Benzamidoaryl)benzohydrols and 6-Chloro-4,4-diphenyl-3,1-benzoxazin-2(4H)-one
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In the reaction of 2-isocyanatobenzoyl chloride (Ia) with phenylmagnesium bromide, the isocyanato group is found to be exclusively attacked by the Grignard reagent to give 2-phenyl-3,1-benzoxazin-4(H)-one (IIIa), N-benzoylanthranilic acid (IVa), N-benzoyl-2-aminobenzophenone (Va), and α-(2-benzamidophenyl)benzohydrol (VIa) depending on the mode of addition and the relative amounts of the Grignard reagent.However, in the case of 5-chloro-2-isocyanatobenzoyl chloride (Ib), the chloroformyl group is also found to react simultaneously, although to a smaller extent, to give 6-chloro-4,4-diphenyl-1,2-dihydro-3,1-benzoxazin-2(4H)-one (VIIb) in addition to 6-chloro-2-phenyl-3,1-benzoxazin-4(H)-one (IIIb), N-benzoyl-2-amino-5-chlorobenzophenone (Vb) and α-(2-benzamido-5-chlorophenyl)benzohydrol (VIb) depending on the reaction conditions.This is presumably due to the decreased reactivity of the isocyanato function due to the chloro group in the para-position.The reaction is believed to proceed through an acyclic intermediate complex which affords IIIa on work-up.PMR data of the compounds have also been discussed.
- Misra, B. K.,Rao, Y. R.,Mahapatra, S. N.
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p. 908 - 911
(2007/10/02)
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