- Ru-Catalyzed C(sp2)?H Bond Arylation of Benzamides Bearing a Novel 4-Aminoantipyrine as a Directing Group
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A novel design-based removable N,O-bidentate directing group based on cheap and commercially available 4-aminoantipyrine (AAP) is reported. Aromatic AP amides bearing 4-aminoantipyrine underwent efficient Ru-catalyzed C(sp2)?H arylation using [RuCl2(PPh3)3] as a catalyst and aryl bromides as electrophiles. The novel bidentate directing group enabled the C?H functionalization reaction with good scope, good functional group tolerance and in decent yields.
- Al Mamari, Hamad H.,Al Kiumi, Diana,Al Rashdi, Tamadher,Al Quraini, Huda,Al Rashdi, Malak,Al Sheraiqi, Sumayya,Al Harmali, Sara,Al Lamki, Mohammed,Al Sheidi, Ahmed,Al Zadjali, Asma
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supporting information
p. 3598 - 3603
(2021/07/22)
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- Mechanochemical Activation of the Reaction of Tetraacetylglycoluril with Some Cyclic Primary Amines. Synthesis of Acetamides
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A new mechanochemical method has been proposed for the synthesis of some acetamides containing a cyclic fragment by reaction of primary cyclic amines with tetraacetylglycoluril.
- Bakibaev,Khoang,Mamontov
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p. 668 - 669
(2018/06/11)
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- Detailed investigation of anticancer activity of sulfamoyl benz(sulfon)amides and 1H–pyrazol–4–yl benzamides: An experimental and computational study
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Cancer is the second leading cause of mortality worldwide. Therapeutic approach to cancer is a multi-faceted one, whereby many cellular/enzymatic pathways have been discovered as important drug targets for the treatment of cancer. A major disadvantage of most of the currently available anticancer drugs is their non-selective cytotoxicity towards cancerous as well as healthy cells. Another major hurdle in cancer therapy is the development of resistance to anticancer drugs. This necessitates the discovery of new molecules with potent and selective cytotoxic activity towards only cancerous cells, with minimum or no damage to the normal/healthy cells. Herein we report detailed investigation into the anticancer activity of sulfamoyl benz(sulfon)amides (1a-1g, 2a-2k) and 1H–pyrazol–4–yl benzamides (3a-3j) against three cancer cell lines, breast cancer cells (MCF–7), bone-marrow cancer cells (K–562) and cervical cancer cells (HeLa). For comparison, screening against healthy baby hamster kidney cells (BHK-21) was carried out. All compounds exhibited selective cytotoxicity towards cancerous cells. Cell cycle analysis was carried out using flow cytometry, followed by fluorescence microscopic analysis. DNA interaction and docking studies were also carried out.
- Iqbal, Jamshed,Ejaz, Syeda Abida,Saeed, Aamer,al-Rashida, Mariya
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- Antinociceptive activity of metamizol metabolites in a rat model of arthritic pain
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Preclinical Research The aim of the present study was to evaluate the antinociceptive activity of the main metamizol (MET) metabolites, 4-methylaminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA), and 4-acetylaminoantipyrine (AAA) using the "pain-induced functional impairment in rat" model (PIFIR model). The antinociceptive efficacies of MAA and AA were 288.3% h and 281.1% h, respectively, close to the efficacy of MET (333.80% h). The effective dose to attain 50% of the maximum response (ED50) values for MET, MAA and AA were 126.1, 124.9, and 110.7 mg/kg, respectively. FAA and AAA were essentially inactive in this experimental model. Part of the antinociceptive effect showed by MET in this study might be attributed to the effect of the metabolites MAA and AA on cyclooxygenases COX-1 and COX-2 activity.
- Lopez-Munoz, Francisco Javier,Soria-Arteche, Olivia,Lopez, Jose Raul Medina,Hurtado Y De La Pena, Marcela,Garcia, Ma. Concepcion Lozada,Moreno-Rocha, Luis Alfonso,Dominguez-Ramirez, Adriana Miriam
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p. 332 - 338
(2013/08/23)
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- Design and synthesis of some new thiophene, thienopyrimidine and thienothiadiazine derivatives of antipyrine as potential antimicrobial agents
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4-acetamide pyrazolone 2 was synthesized by acetylation of 4-amino antipyrine 1 in excellent yield. 4-acetamide pyrazolone 2 was exploited as a starting material for the syntheses of hitherto unknown different types of new heterocyclic compounds incorporating the antipyrine moiety which expect highly biological activity against various microorganisms. Thus, Claisen condensation of 4-acetamide pyrazolone 2 with diethyl oxalate have been utility to afford new 4-oxaloacetyl antipyrine 3, which upon hydrazinolysis of the ester function to obtain the acetohydrazide derivative 18 which used as starting material to synthesize 1,2,4-triazol 19 and hydrazone 20 derivatives. 4-aminothiophene carboxylate derivatives 6, 7 were synthesized by utility of Gewald reaction. On the other hand, Michael type addition of the enolate ion of acetyl functions in acetamide pyrazolone 2 to the activated double bond in arylidenemalonoester to furnish pyrane derivative 9 was done. Finally, 4-acetamide pyrazolone 2 was treated with aromatic substituted aldehyde to exhibit thiophenacrylamide derivative 10. Compound 6 gave characteristic reaction for enaminonitriles, thus, the behavior of o-aminoester of 4-aminothiophene carboxylate derivative 6 toward electrophilic reagent, one carbon donars, amide and acid was also investigated to afford the correspondence thiophene derivatives 11,12,13,15 and 16. In addition, treatment of carboxamide derivative 16 with thionyl chloride afforded the thienothiadiazine derivative 17. The characterization of all synthesized compounds was done by elemental analysis and spectral studies. Moreover, all the synthesized compounds were tested against antimicrobial activities by the disc diffusion method, which exhibited higher promising biological activities.
- Aly, Hala M.,Saleh, Nashwa M.,Elhady, Heba A.
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experimental part
p. 4566 - 4572
(2011/11/05)
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- NMR-derived models of amidopyrine and its metabolites in complexes with rabbit cytochrome P450 2B4 reveal a structural mechanism of sequential N-dealkylation
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To understand the molecular basis of sequential N-dealkylation by cytochrome P450 2B enzymes, we studied the binding of amidopyrine (AP) as well as the metabolites of this reaction, desmethylamidopyrine (DMAP) and aminoantipyrine (AAP), using the X-ray crystal structure of rabbit P450 2B4 and two nuclear magnetic resonance (NMR) techniques: saturation transfer difference (STD) spectroscopy and longitudinal (T1) relaxation NMR. Results of STD NMR of AP and its metabolites bound to P450 2B4 were similar, suggesting that they occupy similar niches within the enzyme's active site. The model-dependent relaxation rates (RM) determined from T1 relaxation NMR of AP and DMAP suggest that the N-linked methyl is closest to the heme. To determine the orientation(s) of AP and its metabolites within the P450 2B4 active site, we used distances calculated from the relaxation rates to constrain the metabolites to the X-ray crystal structure of P450 2B4. Simulated annealing of the complex revealed that the metabolites do indeed occupy similar hydrophobic pockets within the active site, while the N-linked methyls are free to rotate between two binding modes. From these bound structures, a model of N-demethylation in which the N-linked methyl functional groups rotate between catalytic and noncatalytic positions was developed. This study is the first to provide a structural model of a drug and its metabolites complexed to a cytochrome P450 based on NMR and to provide a structural mechanism for how a drug can undergo sequential oxidations without unbinding. The rotation of the amide functional group might represent a common structural mechanism for N-dealkylation reactions for other drugs such as the local anesthetic lidocaine.
- Roberts, Arthur G.,Sjoegren, Sara E. A.,Fomina, Nadezda,Vu, Kathy T.,Almutairi, Adah,Halpert, James R.
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experimental part
p. 2123 - 2134
(2012/03/10)
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- Studies on new cyclic imides obtained from aminophenazone with analgesic properties / Potent effects of a 3,4-dichloromaleimide derivative
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This paper describes the synthesis of new cyclic imides obtained by reaction with aminophenazone (CAS 58-15-1, 4-aminoantipyrine) and different anhydrides with further cyclization with acetic acid under reflux. Their Structures were confirmed by spectral data (IR and NMR) and elemental analysis. The analgesic activity of the synthesized compounds was investigated initially with the writhing test in mice and the most promising compound, a 3,4-dichloromaleimide derivative (3), was analyzed using other models of nociception. The results indicated that compound 3 exerts potent analgesic activity in mice, being more active than some reference drugs. The analgesia caused by this compound was not reversed by naloxone in the writhing test. In the hotplate test, compound 3 did not increase the latency period of pain induced by thermal stimuli, confirming that it does not interact with opioid systems.
- De Campos, Fatima,Correa, Rogerio,De Souza, Marcia Maria,Yunes, Rosendo Augusto,Nunes, Ricardo Jose,Cechinel-Filho, Valdir
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p. 455 - 461
(2007/10/03)
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- THORIUM(IV) AND DIOXOURANIUM(VI) COMPLEXES OF 4-ANTIPYRINE
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A series of new complexes of thorium(IV) and dioxouranium(VI) with 4-antipyrine (AAAP) of the general composition ThX4*2AAAP (X = Cl, Br, NO3 or NCS), ThX4*3AAAP (X = I or ClO4), UO2X2*2AAAP (X = Cl, Br, I, NO3, NCS) or UO2(ClO4)2*3AAAP have been isolated in the solid state.The electrical conductance indicates that except thorium(IV) perchlorate, iodide and dioxouranium(VI) perchlorate complexes, all are non-electrolytes; while Th(ClO4)4*3AAAP behaves as 1:4 electrolyte and ThI4*3AAAP and UO2(ClO4)2*3AAAP are 1:2 electrolytes.The IR spectra show that in all complexes the ligand coordinates the metal via the pyrazolone carbonyl oxygen and amide oxygen atoms.The probable coordination number of Th(IV) is 6, 8 or 12 and of U(VI) is 8 or 10 depending on the nature of anions.Thermal properties are also discussed.
- Agarwal, R. K.
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p. 369 - 377
(2007/10/02)
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