- Design, synthesis, biological evaluation, and molecular docking study on triazine based derivatives as anti-inflammatory agents
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In an attempt to develop new anti-inflammatory agents, design, synthesis, pharmacological activities, and docking study of two groups of triazine-based derivatives were reported. Nine compounds (5a-5d and 10a-10e) consisting of triazine, vanillin, and phenylpyrazole were synthesized through the pharmacophore hybridization method. After confirmation of the structure of the synthesized compounds using spectroscopic methods (FT-IR, and NMR spectral data), their anti-inflammatory activity was evaluated using carrageenan-induced paw edema model in male Wistar rats (200–220 g) administered intraperitoneally at doses of 100 and 200 mg/kg. A group of rats received indomethacin (10 mg/kg) as the standard drug. Among compounds 5a to 5d, only compounds 5c and 5d showed a significant anti-inflammatory effect (p 0.01). Also compound 10a at a dose of (200 mg/kg) and compounds 10b, 10c, 10d and 10e at both doses showed significant anti-inflammatory activity and this effect for 10a (200 mg/kg) and both doses of 10b and 10e was comparable with indomethacin. While indomethacin reduced paw edema by 90%, 10b as the most potent tested compound reduced edema by 93%. The synthesized compounds were docked into the binding sites of both cyclooxygenase-1- and 2- isoenzymes (COX-1 and COX-2) to explore their binding mode and possible interactions of these ligands.
- Alvani, Mohsen,Asadi, Parvin,Hajhashemi, Valiollah,Khodarahmi, Ghadamali,Rostami, Mahboubeh
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Read Online
- Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives
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A novel series of 4-pyrazolyl-1,8-naphthalimide derivatives have been designed and facilely synthesized. For anticancer activity in vitro, most of the compounds were found to be more toxic against human mammary cancer cells (MCF-7) than human cervical car
- Li, Shenghui,Xu, Shengjie,Tang, Yonghe,Ding, Shan,Zhang, Jinchao,Wang, Shuxiang,Zhou, Guoqiang,Zhou, Chuanqi,Li, Xiaoliu
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Read Online
- Pd-EDTA as an efficient catalyst for Suzuki-Miyaura reactions in water
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PdCl2-EDTA complex 1 is an efficient catalyst for the Suzuki-Miyaura reactions of aryl and heteroaryl halides with aryl(heteroaryl)boronic acids in water at 20-100°C. Aryl iodides and bromides undergo the cross-coupling with turnover numbers (T
- Korolev, Dmitrii N.,Bumagin, Nikolay A.
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Read Online
- PHD INHIBITOR COMPOUNDS, COMPOSITIONS, AND USE
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The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (A), and sub-formulas thereof: or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatment of diseases including heart ( e.g. ischemic heart disease, congestive heart failure, and valvular heart disease), lung (e.g., acute lung injury, pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), liver (e.g. acute liver failure and liver fibrosis and cirrhosis), and kidney (e.g. acute kidney injury and chronic kidney disease) disease.
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Paragraph 0781; 0783-0784
(2021/09/26)
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- Visible-Light-Mediated N-Desulfonylation of N-Heterocycles Using a Heteroleptic Copper(I) Complex as a Photocatalyst
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A photoredox protocol that uses a heteroleptic Cu (I) complex, [Cu(dq)(BINAP)]BF4, has been developed for the photodeprotection of benzenesulfonyl-protected N-heterocycles. A range of substrates was examined, including indazoles, indoles, pyrazoles, and benzimidazole, featuring both electron-rich and electron-deficient substituents, giving good yields of the N-heterocycle products with broad functional group tolerance. This transformation was also found to be amenable to flow reaction conditions.
- Hunter, Cameron J.,Boyd, Michael J.,May, Gregory D.,Fimognari, Robert
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p. 8732 - 8739
(2020/07/16)
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- Denitrogenative Pd/Cu-catalyzed Suzuki-type Cross-coupling of Aryltrifluoroborates with Arylhydrazine Hydrochlorides in Water under Room Temperature
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A water-soluble palladium-catalyzed Suzuki-type cross-coupling of aryltrifluoroborates with arylhydrazide hydrochlorides was efficiently developed under mild and environmentally benign conditions, in water without any ligand. The newly developed Pd/Cu co-catalyzed denitrogenative reaction gave a range of structurally diverse substituted biaryls with good to excellent yields, in which the byproduct was nitrogen.
- Wang, Guofang,Meng, Mengting,Deng, Liping,Cheng, Kai,Qi, Chenze
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- Preparation method of pyrazole-4-aryl derivative
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The invention discloses a preparation method of a pyrazole-4-aryl derivative. The preparation method comprises the following step: mixing an aryl halide derivative, a pyrazole-4-boronic acid pinacol ester derivative, first alkali, a first phase transfer catalyst and a first palladium-based catalyst in a first solvent to carry out reaction so as to prepare the pyrazole-4-aryl derivative. Through the manner, the pyrazole-4-aryl derivative is prepared through the adoption of a one-pot method; the reaction condition is mild and the post-treatment is simple and convenient, so that the method is suitable for multiple aryl halide derivatives, strong in operability and suitable for industrial production; and the obtained pyrazole compound can be widely applied to the field of chemical engineering,medicines, biology and materials.
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Paragraph 0017
(2019/01/07)
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- Ligand-free Suzuki-Miyaura coupling using ruthenium(0) nanoparticles and a continuously irradiating microwave system
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We developed a conceptually and methodologically novel ruthenium(0) nanoparticle catalyst, sulfur-modified Au-supported ruthenium nanoparticles (SARu). SARu is easily prepared through a three-step procedure involving simultaneous in situ metal nanoparticle and nanospace organization. This unique method does not require any conventional preformed template to immobilize and stabilize metal nanoparticles. SARu is an ideal ruthenium catalyst for liquid-phase combinatorial synthesis because it repeatedly catalyzes ligand-free Suzuki-Miyaura coupling of aryl halides, including aryl chlorides, with arylboronic acids with low Ru leaching. Physical analysis of SARu showed that the active species in these reactions were ruthenium (0) nanoparticles with a size of 1-3 nm. Also, we developed a continuously irradiating microwave methodology, which can first time discriminate the heating effect and the microwave effect in microwave experiments.
- Akiyama, Toshiki,Taniguchi, Takahisa,Saito, Nozomi,Doi, Ryohei,Honma, Tetsuo,Tamenori, Yusuke,Ohki, Yuuta,Takahashi, Naoyuki,Fujioka, Hiromichi,Sato, Yoshihiro,Arisawa, Mitsuhiro
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p. 3357 - 3369
(2017/07/28)
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- AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 324
(2017/12/01)
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- Suzuki-Miyaura cross-coupling reactions of unprotected haloimidazoles
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An efficient protocol for the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of unprotected haloimidazoles is reported. The relatively mild reaction conditions allow for ready access to a wide array of functionalized imidazole derivatives in good to excellent yields. The synthetic utility of this method is demonstrated by the total synthesis of nortopsentin D.
- Tan, Jiajing,Chen, Yonggang,Li, Hongmei,Yasuda, Nobuyoshi
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p. 8871 - 8876
(2015/01/08)
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- Synthesis and biological evaluation of some novel N-arylpyrazole derivatives as cytotoxic agents
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A series of novel N-arylpyrazole derivatives, 5a-5i, were achieved from substituted phenylacetic acid via Vilsmeier-Haack reaction, hydrolysis, condensation, and aromatic substitution reaction. Their chemical structures were confirmed by 1H NMR
- Li, Shenghui,Xu, Shengjie,Ding, Shan,Zhang, Jinchao,Wang, Shuxiang,Li, Xiaoliu
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p. 1459 - 1468
(2014/05/06)
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- Regioselective synthesis of sulfonylpyrazoles via base mediated reaction of diazosulfones with nitroalkenes and a facile entry into withasomnine
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A base mediated reaction of α-diazo-β-ketosulfone with nitroalkenes affords sulfonylpyrazoles as single regioisomers in excellent yield in a one-pot room temperature reaction. Aryl, heteroaryl, styrenyl, alkyl, hydroxymethyl, and hydrazinyl groups could b
- Kumar, Rahul,Namboothiri, Irishi N. N.
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p. 4016 - 4019
(2011/10/03)
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- Synthesis of 3- and 5-formyl-4-phenyl-1H-pyrazoles: Promising head units for the generation of asymmetric imine ligands and mixed metal polynuclear complexes
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Two synthetic methodologies are reported for the generation of 4-phenyl-1H-pyrazoles substituted at the 3- and/or 5-positions. Functionalisation of the 4-position of dimethyl-4-iodo-1-(tetrahydropyran-2-yl)- 3,5-pyrazolecarboxylate (10) to produce dimethyl-4-phenyl-1-(tetrahydropyran-2- yl)-3,5-pyrazolecarboxylate (14) was achieved by a C-C Suzuki-Miyaura cross coupling reaction in water. However, low yields for this reaction led us to develop a second methodology wherein functionalisation of N-(tetrahydropyran-2- yl)-4-phenylpyrazole (18), synthesised from inexpensive phenylacetic acid, with formyl or hydroxymethyl groups was achieved by lithiation methods. The resulting monoaldehydes, 4-phenyl-5-pyrazole carbaldehyde (20) and 5-formyl-3-(2′- tetrahydropyranyloxymethyl)-4-phenyl-1-(tetrahydropyran-2-yl)pyrazole (28), should facilitate access to new, asymmetric, imine ligands based on a 4-phenyl-1H-pyrazole moiety. This was proven by the successful synthesis of the heterometallic tetranuclear complex [FeII(NiIIL 2)3](BF4)2·solvents. Likewise, the alcohol isolated en route to 28, N-(tetrahydropyran-2-yl)-5- (hydroxymethyl)-4-phenylpyrazole (24), should facilitate access to new, asymmetric, amine ligands.
- Olguin, Juan,Brooker, Sally
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experimental part
p. 1242 - 1253
(2011/08/03)
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- Inverse electron demand diels-alder reactions of 1,2,3-triazines: Pronounced substituent effects on reactivity and cycloaddition scope
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A systematic study of the inverse electron demand Diels-Alder reactions of 1,2,3-triazines is disclosed, including an examination of the impact of a C5 substituent. Such substituents were found to exhibit a remarkable impact on the cycloaddition reactivity of the 1,2,3-triazine without altering, and perhaps even enhancing, the intrinsic cycloaddition regioselectivity. The study revealed not only that the reactivity may be predictably modulated by a C5 substituent (R = CO2Me > Ph > H) but also that the impact is of a magnitude to convert 1,2,3-triazine (1) and its modest cycloaddition scope into a heterocyclic azadiene system with a reaction scope that portends extensive synthetic utility, expanding the range of participating dienophiles. Significantly, the studies define a now powerful additional heterocyclic azadiene, complementary to the isomeric 1,2,4-triazines and 1,3,5-triazines, capable of dependable participation in inverse electron demand Diels-Alder reactions, extending the number of complementary heterocyclic ring systems accessible with implementation of the methodology.
- Anderson, Erin D.,Boger, Dale L.
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supporting information; experimental part
p. 12285 - 12292
(2011/09/16)
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- Direct synthesis of pyrazolo[5,1-a]isoindoles via intramolecular palladium-catalyzed C-H bond activation
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An efficient, direct synthesis of pyrazolo-[5,1-a]isoindoles employing a palladium-catalyzed intramolecular C-H bond activation of 1-(2-halobenzyl) pyrazoles has been developed. The use of lithium chloride (LiCl) was found to be essential in these reactions, to suppress further C-H bond activation at the C-3 position of pyrazolo[5,1-a]isoindole, when C-3 is unsubstituted. This protocol can be applied to the synthesis of a pyrazolo[5,1-a]isoquinoline possessing a six-membered central ring system and a fully substituted pyrazolo[5,1-a]isoindole using sequential intra- and intermolecular C-H bond activation.
- Choi, Young Lok,Lee, Hyuk,Kim, Bum Tae,Choi, Kihang,Heo, Jung-Nyoung
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supporting information; experimental part
p. 2041 - 2049
(2010/11/19)
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- Pyrazole synthesis using a titanium-catalyzed multicomponent coupling reaction and synthesis of withasomnine
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The titanium-catalyzed 3-component coupling of an alkyne, isonitrile, and amine can be used to generate tautomers of 1,3-diimines. These diimines produced in situ undergo cyclization with hydrazine and hydrazine derivatives in a one-pot procedure to provi
- Majumder, Supriyo,Gipson, Kevin R.,Staples, Richard J.,Odom, Aaron L.
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experimental part
p. 2013 - 2023
(2011/02/28)
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- Bu3SnH-mediated radical cyclisation onto azoles
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Alkyl radicals have been cyclised onto pyrroles, imidazoles and pyrazoles, and acyl radicals cyclised onto pyrroles, using Bu3SnH-, (TMS)3SiH- and Bu3GeH-mediated aromatic homolytic substitution for the synthesis of bicyclic N-heterocycles. The reactions yield intermediate π-radicals that lose hydrogen in the?rearomatisation step of the aromatic homolytic substitution. Mechanistic studies of these rearomatisation steps indicate aromatic homolytic substitution in which the initiator or breakdown products from the inhibitor are responsible for the H-abstraction step.
- Allin, Steven M.,Barton, William R.S.,Russell Bowman,Bridge (née Mann), Emma,Elsegood, Mark R.J.,McInally, Tom,McKee, Vickie
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p. 7745 - 7758
(2008/12/21)
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- Synthesis of 4-arylpyrazoles via PdCl2(dppf)-catalyzed cross coupling reaction with Grignard reagents
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4-Aryl-l-tritylpyrazoles were prepared from the cross coupling reaction of aryl Grignard reagents with 4-bromo-1-tritylpyrazoles in the presence of 0.2 mol% PdCl2(dppf) as catalyst. To deprotect the trityl group, 4-phenyl-l-tritylpyrazole was r
- Ichikawa, Hayato,Ohno, Yuuki,Usami, Yoshihide,Arimoto, Masao
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p. 2247 - 2252
(2007/10/03)
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- A versatile method for suzuki cross-coupling reactions of nitrogen heterocycles
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(Chemical Equation Presented) A wide-ranging study of Suzuki reactions which use nitrogen-containing heterocycles is described (see scheme; dba = dibenzylideneacetone, Cy = cyclohexyl). This method is highly versatile (a single procedure was used for all substrates, including boronate esters and trifluoroborates), compatible with a variety of unprotected functionalities (e.g., NH2-and OH-substituted substrates), and efficient even with unactivated aryl chlorides.
- Kudo, Noriaki,Perseghini, Mauro,Fu, Gregory C.
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p. 1282 - 1284
(2007/10/03)
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- Pyrazolyl derivatives, preparation process and intermediates of this process as medicinal products and pharmaceutical compositions containing them
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The present invention relates to the novel derivatives of formula (I) in which A is, if it is present, a (C1-C6) alkyl, a (C3-C6) alkenyl, a (C3-C6) alkynyl, a (C3-C7) cycloalkyl or a (C5-C7) cycloalkenyl, R1 is an NR6R7, (C4-C7) azacycloalkyl, (C5-C7) azacycloalkenyl, (C5-C9) azabicycloalkyl or (C5-C9) azabicycloalkenyl group; A-R1 is such that the nitrogen of R1 and the nitrogen in the 1-position of the pyrazole are necessarily separated by at least two carbon atoms, R3 is an H, halogen, OH, SH, NH2, ORc, SRc, SORa, SO2Ra, NHCHO, NRaRb, NHC(O)Ra, NHC(S)Ra or NHSO2Ra, R4 is an aryl or heteroaryl; and R5 is an H, halogen, CF3, CHF2, CH2F, linear or branched (C1-C6) alkyl or (C3-C7) cycloalkyl to their racemates, enantiomers and diastereoisomers and to their mixtures, their tautomers and to their pharmaceutically acceptable salts.
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Page/Page column 46
(2008/06/13)
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- Synthesis of the silver(I) complex of CH2[CH(pz 4Et)2]2 containing the unprecedented [Ag(NO3)4]3- anion: A general method for the preparation of 4-(alkyl)pyrazoles
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A general two-step method for the syntheses of 4-(alkyl)pyrazoles has been developed. The first step involves the reaction between organyl diethylacetals and the Vilsmeier reagent to give a mixture of ethoxy-and dimethylamino- acroleins. This mixture reacts directly with hydrazine monohydrogenchloride to yield the desired (4-substituted)pyrazoles. The 4-(phenyl)pyrazole derivative exhibited a markedly lower solubility in common organic solvents. In the solid state structure the phenyl and pyrazolyl groups are nearly coplanar and extensive intermolecular CH-π interactions organize the molecules in two-dimensional sheets that are held in a three dimensional arrangement by NH...N hydrogen bonds. Tetrakis[(4-ethyl)pyrazolyl]propane, CH 2[CH(pz4Et)2]2, was prepared by a transamination reaction and reacts with Ag(NO3) to yield a compound with a 4:3 metal:ligand mole ratio that when crystallized by diffusion of Et2O into an acetone solution produced [Ag2{μ-CH 2[CH(pz4Et)2]2}2] 3[Ag(NO3)4]2 (1). This complex contains dimeric units in which two silver cations are sandwiched between two CH2[CH(pz4Et)]2 ligands and the counterion is the unprecedented tetra(nitrato)argentate anion. ESI mass spectral data support the existence of both the cationic dimeric units and the [Ag(NO 3)4]- anion in solution.
- Reger, Daniel L.,Gardinier, James R.,Grattan, T. Christian,Smith, Monica R.,Smith, Mark D.
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p. 1670 - 1677
(2007/10/03)
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- Radical cyclisation onto pyrazoles: Synthesis of withasomnine
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A novel synthetic protocol for the synthesis of [1,2-b]-fused bicyclic pyrazoles has been developed using radical cyclisation. The protocol uses cyclisation of pyrazole-1-(ω-alkyl) radicals generated from 1-[ω-(phenylselenyl)alkyl]-pyrazole precursors. The pyrazole natural product, withasomnine (3-phenyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole), and larger ring analogues have been synthesised in good yield using the protocol. A Bu3SnH-mediated oxidative cyclisation mechanism is facilitated by azo or Et3B radical initiators acting as oxidants of the intermediate π-radicals.
- Allin, Steven M.,Barton, William R.S.,Bowman, W.Russell,McInally, Tom
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p. 4191 - 4193
(2007/10/03)
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- Synthesis and reactions of some ethyl 3-aroyl-4-aryl-2-pyrazoline-5-carboxylates
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A series of ethyl 3-aroyl-4-aryl-2-pyrazoline-5-carboxylates 1 was prepared. Their reactions with bromine water, potassium permanganate and potassium hydroxide afforded the corresponding pyrazoles. With aryl and aroyl hydrazines the pyrazolines 1 gave the Schiff bases 9 while with hydrazine hydrate they yielded the corresponding acid hydrazides 11. Condensation of 11 with aromatic aldehydes gave the arylidene derivatives 12, which on cyclization with the proper reagent afforded 13 or 14. Reaction of 1 with hydrochloric acid gave the corresponding dipyrazolo-pyrazine derivatives 10.
- Faidallah,Makki,Elmassry,Hassan
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p. 101 - 105
(2007/10/03)
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- Synthesis and reactions of some ethyl 3(5)aroyl-4-aryl-2-pyrazoline-5(3)carboxylates
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A series of ethyl 3(5)aroyl-4-aiyl-2-pyrazoline-5(3)carboxylates 1 was prepared. Their reactions with bromine water, potassium permanganate and potassium hydroxide afforded the corresponding pyrazoles. With aryl and aroyl hydrazines the pyrazolines 1 gave the Schiff bases 9 while with hydrazine hydrate they yielded the corresponding acid hydrazides 11. Condensation of 11 with aromatic aldehydes gave the arylidene derivatives 12, which, on cyclization with the propar reagent, afforded 13 or 14. Reaction of 1 with hydrochloric acid gave the corresponding dipyrazolo-pyrazine derivatives 10.
- Faidallah, Hassan M.,Makki, Mohamed S. I.,El-Massry, Abdel-Moneium I.,Hassan, Saham Y.
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p. 1141 - 1153
(2007/10/03)
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- 3,4, or 5-aryl-1H-pyrazole-1-alkanamides as antiarrhythmic agents, compositions and use
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N-[(disubstituted amino)alkyl]-3,4 or 5-aryl-1H-pyrazole-1-acetamides, useful for treating cardiac arrhythmias in mammals, are prepared by reacting a lower-alkyl ester of pyrazole-1-acetic acid with an appropriate diamine.
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- HETEROCYCLE FORMATION FROM 1,3-DINITROALKANES. A NOVEL PYRAZOLE SYNTHESIS
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1,3-Dinitroalkanes, obtained in almost quantitative yields by Michael additions of nitroalkanes to nitro-olefins, react with hydrazines affording pyrazoles, in most cases in high yields.
- Escribano, F. Cabrera,Alcantara, M. P. Derri,Gomez-Sanchez, A.
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p. 6001 - 6004
(2007/10/02)
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- NEW EFFICIENT SYNTHESIS OF 3(5)-CARBOMETHOXY-4-ARYLPYRAZOLES FROM 3-ARYL-2,3-DEHYDROAMINO ACID DERIVATIVES
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3(5)-Carbomethoxy-4-arylpyrazoles can be easily obtained by aromatization with boron trifluoride etherate of 4-aryl-3-acetamido(or benzamido)-3-carbomethoxy-Δ1-pyrazolines synthesized by 1,3-dipolar cycloaddition of diazomethane with 3-aryl-2,3
- Catiela, Carlos,Villegas, M. Dolores Diaz de,Gainza, M. Pilar
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p. 165 - 172
(2007/10/02)
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- NEW METHODS AND REAGENTS IN ORGANIC SYNTHESIS. 41. LITHIUM TRIMETHYLSILYLDIAZOMETHANE. A NEW SYNTHON FOR THE PREPARATION OF PYRAZOLES FROM α,β-UNSATURATED NITRILES
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Lithium trimethylsilyldiazomethane reacts smoothly with various α,β-unsaturated nitriles to give 3(or 5)-trimethylsilylpyrazoles in good yields.
- Aoyama, Toyohiko,Inoue, Sumie,Shioiri, Takayuki
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p. 433 - 436
(2007/10/02)
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- A SYNTHESIS OF WITHASOMNINE FROM 4-PHENYLPYRAZOLE
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Withasomnine (5), a pyrazole alkaloid isolated from Withania somnifera Dun.(Solanaceae), has been synthesized from 4-phenylpyrazole(1), a compound with potential symmetry.
- Takano, Seiichi,Imamura, Yoko,Ogasawara, Kunio
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p. 1223 - 1225
(2007/10/02)
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