- Identification of potent anticancer copper(ii) complexes containing tripodal bis[2-ethyl-di(3,5-dialkyl-1H-pyrazol-1-yl)]amine moiety
-
A series of heteroleptic copper(ii) complexes of the composition [Cu(L1-5)Cl]X, where X = ClO4 and/or PF6 and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(6-methyl-(2-pyridylmethyl))]amine (L1), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(3,4-dimethoxy-(2-pyridylmethyl))]amine (L2), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(2-quinolymethyl)]amine (L3), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazolyl)-(di(3,5-dimethyl-1H-pyrazol-1-yl-methyl))]amine (L4) and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(5-methyl-3-phenyl-1H-pyrazol-1-yl-methyl)]amine (L5), were prepared and thoroughly characterized including single-crystal X-ray diffraction technique. The in vitro cytotoxicity of complexes against A2780, A2780R, HOS and MCF-7 human cancer cell lines was evaluated using the MTT test. The results revealed that complexes [Cu(L1)Cl]PF6 (1-PF6), [Cu(L2)Cl]ClO4 (2-ClO4) and [Cu(L3)Cl]PF6 (3-PF6) are the most effective, with IC50 values ranging from 1.4 to 6.3 μM, thus exceeding the cytotoxic potential of metallodrug cisplatin (IC50 values ranging from 29.9 to 82.0 μM). The complexes [Cu(L4)Cl]PF6 (4-PF6) and [Cu(L5)Cl]PF6 (5-PF6) showed only moderate cytotoxicity against A2780, with IC50 = 53.6 μM, and 33.8 μM, respectively. The cell cycle profile, time-resolved cellular uptake, interactions with small sulfur-containing biomolecules (cysteine and glutathione), intracellular ROS production, induction of apoptosis and activation of caspases 3/7 were also evaluated in the case of the selected complexes. It has been found that the best performing complexes 1 and 2 cause cell arrest in the G2/M phase and induce apoptosis via the increase in production of ROS, dominantly due to the overproduction of superoxide.
- Dial, Madison T.,Dvo?ák, Zdeněk,Fischer, Roland C.,Louka, Febee R.,Malek, Andrew J.,Malina, Tomá?,Massoud, Salah S.,Mautner, Franz A.,Trávní?ek, Zdeněk,Van?o, Ján
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p. 11521 - 11534
(2021/08/30)
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- Discovery of pyrazole N-aryl sulfonate: A novel and highly potent cyclooxygenase-2 (COX-2) selective inhibitors
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Based on a new pyrazole sulfonate synthetic method, a novel class of molecules with a basic structure of pyrazole N-aryl sulfonate have been designed and synthesized. The interest in conducting intensive research stems from quite evident anti-inflammatory effects exhibited by the compounds in preliminary animal experiments. A series of compounds were synthesized by different substitutions of the R1, R2, and R3 groups. Within the series, 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and phenyl 5-methyl-3-(4-(trifluoromethyl) phenyl)-1H-pyrazole-1-sulfonate exhibited excellent anti-inflammatory activity (% inhibition of auricular edemas = 27.0 and 35.9, respectively); the in vivo analgesic activity of phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate was confirmed to be effective (inhibition ratio of writhing = 50.7% and 48.5% separately), and compounds phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate, 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate were identified as selective COX-2 inhibitors (SI = 455, 10,497 and >189 severally). In Acute Oral Toxicity assays conducted in vivo, the lethal dose 50 (LD50) of 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate to mice was >2000 mg/kg BW.
- Guo, Quanping,Wang, Mengran,Wang, Rui,Xu, Zhaoqing,Yao, Haiyan
-
-
- Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study
-
This report demonstrates the successful application of electrostatic surface potential distribution analysis for evaluating the relative catalytic activity of a series of azolium-based halogen bond donors. A strong correlation (R2> 0.97) was observed between the positive electrostatic potential of the σ-hole on the halogen atom and the Gibbs free energy of activation of the model reactions (i.e., halogen abstraction and carbonyl activation). The predictive ability of the applied approach was confirmed experimentally. It was also determined that the catalytic activity of azolium-based halogen bond donors was generally governed by the structure of the azolium cycle, whereas the substituents on the heterocycle had a limited impact on the activity. Ultimately, this study highlighted four of the most promising azolium halogen bond donors, which are expected to exhibit high catalytic activity.
- Bolotin, Dmitrii S.,Il'in, Mikhail V.,Novikov, Alexander S.,Suslonov, Vitalii V.,Sysoeva, Alexandra A.
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p. 7611 - 7620
(2021/09/22)
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- Cs2CO3-promoted P-N coupling reaction of H-phosphoryl compounds with N-tosylhydrazones to afford N-phosphorylhydrazones via diazo intermediates
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The Cs2CO3-promoted P-N coupling reaction of H-phosphoryl compounds and N-tosylhydrazones is reported. Formally, this transformation represents an interesting example of exchanging the sulfur and phosphorus functionalities to convert
- Li, Xiaojie,Shen, Ruwei,Zhang, Can
-
supporting information
(2021/11/04)
-
- Regiocontrolled Coupling of Alkynes and Dipolar Reagents: Iron-Mediated [3 + 2] Cycloadditions Revisited
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Cyclopentadienyliron dicarbonyl based allenyliron complexes were prepared, and their formal [3 + 2] cycloaddition with a number of dipolar reagents was investigated as a means of preparing heterocyclic compounds in a regiocontrolled manner. In addition, the mechanism of the isomerization of an allenyliron complex to its propargyliron tautomer was investigated. Results in support of both radical and two-electron mechanisms for isomerization are presented.
- Zhu, Jin,Durham, Austin C.,Wang, Yidong,Corcoran, James C.,Zuo, Xiao-Dong,Geib, Steven J.,Wang, Yi-Ming
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supporting information
p. 2295 - 2304
(2021/05/06)
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- Nano-SnCl4 /SiO2 as a catalyst for one-pot synthesis of substituted 1h-pyrazoles as antifungal and cytotoxic agents
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A simple and efficient method was developed for the synthesis of pyrazole derivatives via a one-pot reaction of 1,3-diketone and substituted hydrazines in the presence of nano-SnCl4/SiO2 as a mild catalyst. A series of some pyrazole derivatives (P1-P11) was synthesized and evaluated as anti-fungal and anti-cancer agents. Compounds P10 and P11 were demonstrated. The antimicrobial activities of the synthetic compounds showed that compounds P10 and P11 most excellently inhibited the growth of dermatophytes or Aspergillus species, respectively. Therefore, the cytotoxic activities of the-se compounds on two human cancer cell lines, A549 (lung cancer) and MCF-7 (breast cancer) were further assessed. Hence, results demonstrated that beside antifungal activity, P10 had also desirable cy-totoxic effect on investigated cancerous cell lines, even higher than cisplatin.
- Faghih, Zeinab,Khabnadideh, Soghra,Mirjalili, Bi Bi Fatemeh,Moradi, Hadi,Zamani, Leila,Zomorodian, Kamiar
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p. 459 - 465
(2020/04/21)
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- Heck Reactions of Acrolein or Enones and Aryl Bromides – Synthesis of 3-Aryl Propenals or Propenones and Consecutive Application in Multicomponent Pyrazole Syntheses
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3-(Hetero)aryl propenals or propenones are efficiently prepared by a Heck reaction of (hetero)aryl bromides and acrolein or vinyl ketones using Beller's CataCXium Ptb ligand under Jeffery's and Fu's conditions. The formation of these three-carbon building blocks is embedded into consecutive three- and pseudo-four-component syntheses of 3-(hetero)aryl and 3,5-diarylpyrazoles with a broad substitution pattern in moderate to excellent yield.
- Stephan, Marvin,Panther, Jesco,Wilbert, Fabio,Ozog, Pauline,Müller, Thomas J. J.
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p. 2086 - 2092
(2020/03/23)
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- Sunlight-promoted Direct Irradiation of N-centred Anion: The Photocatalyst-free Synthesis of Pyrazoles in Water
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A practical method through sunlight mediated annulation of α,β-unsaturated hydrazones has been developed for the synthesis of pyrazole. Based on the analysis of UV-Vis absorption of the substrate, the reaction was designed to avoid the use of external photocatalysis and proceeds via direct irradiation of N-centred anion by sunlight. The key features of this reaction include operational simplicity, readily available reagents, and amenability to gram-scale synthesis. (Figure presented.).
- Zhang, Te,Meng, Yunge,Lu, Jinye,Yang, Yuting,Li, Gong-Qiang,Zhu, Chunyin
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supporting information
p. 3063 - 3068
(2017/12/04)
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- An Efficient Synthesis of Substituted Pyrazoles from One-Pot Reaction of Ketones, Aldehydes, and Hydrazine Monohydrochloride
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An efficient, one-pot and metal-free process for the preparation of 3,5-disubstituted and 3,4,5-trisubstituted pyrazoles on multi-gram scale was developed. One-pot condensation of ketones, aldehydes and hydrazine monohydrochloride readily formed pyrazoline intermediates under mild conditions. Oxidation of pyrazolines, in situ, employing bromine afforded a wide variety of pyrazoles. The methodology offers a fast, and often chromatography-free protocol for the synthesis of 3,4,5-substituted pyrazoles in good to excellent yields. Alternatively, a more benign oxidation protocol affords 3,5-disubstituted or 3,4,5-trisubstituted pyrazoles by simply heating pyrazolines in DMSO under oxygen.
- Lellek, Vit,Chen, Cheng-Yi,Yang, Wanggui,Liu, Jie,Ji, Xuebao,Faessler, Roger
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supporting information
p. 1071 - 1075
(2018/02/26)
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- Discovery of DS79182026: A potent orally active hepcidin production inhibitor
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Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of benzisoxazole compounds as orally active hepcidin production inhibitors. The optimization study of multi kinase inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.
- Fukuda, Takeshi,Goto, Riki,Kiho, Toshihiro,Ueda, Kenjiro,Muramatsu, Sumie,Hashimoto, Masami,Aki, Anri,Watanabe, Kengo,Tanaka, Naoki
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p. 3716 - 3722
(2017/07/27)
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- Nano-TiO2: An efficient and reusable catalyst for the synthesis of 1,3,5-substituted pyrazoles
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(Formula presented) A Nano-TiO2 is an efficient catalysis for the synthesis of 1,3,5-substituted pyrazoles via condensation of 1,3- diketones and hydrazines. Simple procedure, mild heating, solvent free, high yielding, and easy workup are some advantages of this protocol. The catalyst can be recovered easily and reused many times without significant loss in catalytic activity and selectivity.
- Akbari, Ali,Mirjalili, Bibi Fatemeh
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p. 119 - 123
(2016/07/15)
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- Pyrazole-Based Acid Ceramidase Inhibitors: Design, Synthesis, and Structure-Activity Relationships
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Acid ceramidase (AC) is a lysosomal cysteine amidase responsible for the cleavage of ceramide into sphingosine, which is then phosphorylated to sphingosine 1-phosphate. AC regulates the intracellular levels of ceramide and sphingosine, and AC inhibition may be useful in the treatment of disorders, such as cancer, in which ceramide-mediated signaling may be dysfunctional. Despite their potential experimental and therapeutic value, the number of available small-molecule inhibitors of AC activity remains limited. In the present study is described the discovery of a class of potent pyrazole carboxamide-based AC inhibitors, which were identified using the atomic property field (APF) approach and developed through systematic SAR investigations and in vitro pharmacological characterization. The best compound of this series inhibits AC with nanomolar potency and causes ceramide accumulation and sphingosine depletion in intact G361 proliferative melanoma cells. By expanding the current armamentarium of AC inhibitors, these results should facilitate future efforts to unravel the biology of AC and the therapeutic potential of its inhibition.
- Diamanti, Eleonora,Bottegoni, Giovanni,Goldoni, Luca,Realini, Natalia,Pagliuca, Chiara,Bertozzi, Fabio,Piomelli, Daniele,Pizzirani, Daniela
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supporting information
p. 2739 - 2756
(2016/08/31)
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- A facile and expeditious approach to substituted 1H-pyrazoles catalyzed by iodine
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A facile and expeditious method for the synthesis of 1H-pyrazoles by the reaction of α,β-unsaturated aldehydes/ketones and sulfonyl hydrazide catalyzed by as low as 2 mol % I2 has been demonstrated. This synthetic system features simple operation and mild reaction conditions, and displays a broad functional group tolerance furnishing good to excellent yields.
- Zhang, Hailei,Wei, Qian,Zhu, Guodong,Qu, Jingping,Wang, Baomin
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supporting information
p. 2633 - 2637
(2016/06/01)
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- PRODUCING METHOD OF NITROGEN-CONTAINING ORGANIC COMPOUND
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A hydrazine-carbon dioxide-binding compound or hydrazine derivatives 2 carbonyl group react with a compound having one or more nitrogen-containing organic for preparing the compounds of relates to method.
- -
-
Paragraph 0273-0257
(2016/12/01)
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- A modified and practical synthetic route to indazoles and pyrazoles using tungstate sulfuric acid
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Tungstate sulfuric acid-catalyzed Knorr reaction have been used as a simple, rapid, atom economic and green method for the synthesis of indazole and pyrazole derivatives based on the condensation of hydrazine derivatives and ss-dicarbonyl compounds under solvent-free conditions. It was found that the catalyst could be recovered and reused without significant loss of its activity. The use of this method provides a novel and improved modification of Knorr synthesis in terms of clean reaction profile, use of a safe catalyst and solvent-free conditions. A green method for the synthesis of indazole and pyrazole derivatives from the condensation of hydrazine derivatives with dicarbonyl compounds has been described. Tungstate sulfuric acid (TSA) catalyzed efficiently the reactions to give good yields.
- Rahmatzadeh, S. Setareh,Karami, Bahador,Khodabakhshi, Saeed
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- Electrophilic alkylation of pseudotetrahedral nickel(II) arylthiolate complexes
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A kinetic study is reported for reactions of pseudotetrahedral nickel(II) arylthiolate complexes [(TpR,Me)Ni-SAr] (TpR,Me = hydrotris{3-R-5-methyl-1-pyrazolyl}borate, R = Me, Ph, and Ar = C6H5, C6H4-4-Cl, C6H4-4-Me, C6H4-4-OMe, 2,4,6-Me3C6H2, 2,4,6-iPr3C6H2) with organic electrophiles R'X (i.e., MeI, EtI, BzBr) in low-polarity organic solvents (toluene, THF, chloroform, dichloromethane, or 1,2-dichloroethane), yielding a pseudotetrahedral halide complex [(TpR,Me)Ni-X] (X = Cl, Br, I) and the corresponding organosulfide R'SAr. Competitive reactions with halogenated solvents and adventitious air were also examined. Akin to reactions of analogous and biomimetic zinc complexes, a pertinent mechanistic question is the nature of the reactive nucleophile, either an intact thiolate complex or a free arylthiolate resulting from a dissociative pre-equilibrium. The observed kinetics conformed to a second-order rate law, first order with respect to the complex and electrophile, and no intermediate complexes were observed. In the absence of a mechanistically diagnostic rate law, a variety of mechanistic probes were examined, including kinetic effects of varying the metal, solvent, electrophile, and temperature, as well as the 3-pyrazolyl and arylthiolate substituents. Compared to zinc analogues, the effect of Ni-SAr covalency is also of interest herein. The results are broadly interpreted with respect to the disparate mechanistic pathways.
- Deb, Tapash,Jensen, Michael P.
-
supporting information
p. 87 - 96
(2015/03/03)
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- 2-(1H-Pyrazol-1-yl)acetic acids as chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes (CRTh2) antagonists
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In this manuscript, the synthesis and biological activity of a series of pyrazole acetic acid derivatives as CRTh2 antagonists is presented. Biological evaluation in vitro revealed that the pyrazole core showed in several cases a different structure-activity relationship (SAR) to that of related indole acetic acid. A potent series of ortho-sulfonyl benzyl substituents was found, from which compounds 27 and 63 were advanced to in vivo profiling.
- Andrés, Miriam,Bravo, Mónica,Buil, Maria Antonia,Calbet, Marta,Castillo, Marcos,Castro, Jordi,Eichhorn, Peter,Ferrer, Manel,Lehner, Martin D.,Moreno, Imma,Roberts, Richard S.,Sevilla, Sara
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p. 168 - 184
(2014/01/06)
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- Copper-catalyzed intermolecular C-H amination of (Hetero)arenes via transient unsymmetrical λ3-iodanes
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A one-pot two-step method for intermolecular C-H amination of electron-rich heteroarenes and arenes has been developed. The approach is based on a room-temperature copper-catalyzed regioselective reaction of the in situ formed unsymmetrical (hetero)aryl-λ3-iodanes with a wide range of primary and secondary aliphatic amines and anilines.
- Sokolovs, Igors,Lubriks, Dmitrijs,Suna, Edgars
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p. 6920 - 6928
(2014/06/09)
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- Palladium-catalysed carbonylative α-arylation of acetone and acetophenones to 1,3-diketones
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Three COmponent α-arylation: A carbonylative ketone α-arylation process employing acetone for the first time, as well as acetophenones, is described (see scheme). The reaction tolerates a range of (hetero)aryl iodides and several functionalised aryl ketone coupling partners. Only low pressures of molecular CO are applied and no additional solvent is necessary. Copyright
- Schranck, Johannes,Tlili, Anis,Alsabeh, Pamela G.,Neumann, Helfried,Stradiotto, Mark,Beller, Matthias
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supporting information
p. 12624 - 12628
(2013/10/01)
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- Facile and efficient regioselective synthesis of 1-(3′-substituted quinoxalin-2′-yl)-3-aryl/heteroaryl-5-methylpyrazoles
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This report describes an efficient and practical approach for regioselective synthesis of 1-(3′-substituted quinoxalin-2′-yl)-3- aryl/heteroaryl-5-methylpyrazoles (3a-j). Reaction of 2-chloro-3-substituted quinoxalines (1) with 3(5)-methyl-5(3)-aryl-1H-pyrazoles (2) in the presence of sodium hydride furnished the title compounds in excellent yields with good levels of regioselectivity. The present protocol is superior to the existing method, which yielded a mixture of regioisomeric pyrazoles (I, II) and triazolo[4,3-a]quinoxalines (III). Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Aggarwal, Ranjana,Masan, Eakta,Sumran, Garima
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p. 1842 - 1848
(2013/05/21)
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- Efficient one-pot synthesis of substituted pyrazoles
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An efficient, one-pot synthesis of substituted pyrazoles from enones, hydrazides, and halides was developed. In comparison with the classical Knorr pyrazole synthesis, this methodology gave a different type of product (R 3≥R5). A range of substituted pyrazoles were prepared in good to high yields with complete regioselectivity.
- Tang, Meng,Zhang, Fu-Min
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p. 1427 - 1433
(2013/02/25)
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- A simple and efficient synthesis of pyrazoles in water
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A simple, highly efficient, and environmentally friendly method for the synthesis of substituted 1H-pyrazoles by one-pot condensation reaction of α,β-unsaturated carbonyl compounds with tosyl hydrazide in water was developed. The reaction system exhibited tolerance with various functional groups, Aromatic moiety with both electron-rich and electron-deficient substituents could give desired products in good to excellent yields.
- Wen, Jun,Fu, Yun,Zhang, Ruo-Yi,Zhang, Ji,Chen, Shan-Yong,Yu, Xiao-Qi
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supporting information; experimental part
p. 9618 - 9621
(2011/12/14)
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- Synthesis of dienes by palladium-catalyzed couplings of tosylhydrazones with aryl and alkenyl halides
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Two different combinations of coupling partners can be employed for the synthesis of conjugated dienes by palladium-catalyzed cross-coupling with tosylhydrazones: α,β-unsaturated ketone and aryl halide or alkenyl halide and non-conjugated tosylhydrazone. Depending on the substrate, a vinylogous hydride elimination is responsible for the formation of the final dienes. Copyright
- Barluenga, Jose,Tomas-Gamasa, Maria,Aznar, Fernando,Valdes, Carlos
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scheme or table
p. 3235 - 3240
(2011/02/28)
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- PYRAZOLYL SUBSTITUTED CARBONIC ACID DERIVATIVES AS MODULATORS OF THE PROSTACYCLIN(PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
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Pyrazole derivatives of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH) and related disorders; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).
- -
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Page/Page column 124
(2010/07/02)
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- Design, synthesis and analgesic properties of novel conformationally-restricted N-acylhydrazones (NAH)
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A set of six azaheterocycles were designed as conformationnaly-constrained N-acylhydrazones and tested as analgesics.
- Kuemmerle, Arthur E.,Vieira, Marina M.,Schmitt, Martine,Miranda, Ana L.P.,Fraga, Carlos A.M.,Bourguignon, Jean-Jacques,Barreiro, Eliezer J.
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scheme or table
p. 4963 - 4966
(2010/03/24)
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- NITROGENATED HETEROCYCLIC COMPOUND AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to novel compounds having a xanthine oxidase inhibitory effect and an uricosuric effect and pharmaceutical compositions comprising the same as an active ingredient. That is, the present invention relates nitrogen-containing heterocyclic compounds represented by the following general formula (I): wherein Y1 represents N or C(R4) ; Y2 represents N or C(R5) ; R4 and R5 independently represent an alkyl group, a hydrogen atom etc. ; one of R1 and R2 represents an optionally substituted aryl group, an alkoxygroup or an optionally substituted heterocyclic group; the other of R1 and R2 represents a haloalkyl group, a cyanogroup, ahalogenatometc.; and R3 represents a 5-tetrazolyl group or a carboxy group, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising the same as an active ingredient.
- -
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Page/Page column 6; 8
(2008/12/06)
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- HETEROCYCLIC COMPOUNDS AS MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS, USEFUL FOR THE TREATMENT AND/OR PREVENTION OF DISORDERS MODULATED BY A PPAR
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The present invention is directed to a compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate or stereoisomer thereof, which is useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.
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Page/Page column 80
(2010/02/11)
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- Regioselective formation of N-alkyl-3,5-pyrazole derived ligands. A synthetic and computational study
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New N-alkyl-3,5-pyrazole derived ligands were synthesized by reaction between 3,5-pyrazole derived ligands and the appropriate haloalkane in toluene or THF using NaOEt or NaH as base. When the precursor ligand bears a pyridyl substituent the alkylation reaction presents a large regioselectivity. Theoretical calculations have been carried out to rationalize the experimental observations. It has been shown that regioselectivity is governed by the formation of Na+-pyrazolide chelate complexes.
- Montoya, Vanessa,Pons, Josefina,Branchadell, Vicen?,Ros, Josep
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p. 12377 - 12385
(2007/10/03)
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- Reactivity studies of (η6-arene)ruthenium dimeric complexes towards pyrazoles: Isolation of amidines, bis pyrazoles and chloro bridged pyrazole complexes
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The complex [(η6-p-cymene)Ru(μ-Cl)Cl]2 1 reacts with pyrazole ligands (3a-g) in acetonitrile to afford the amidine derivatives of the type [(η6-p-cymene)Ru(L) (3,5-HRR′pz)](BF4)2 (4a-f), where L = {HN = C(Me)3,5-RR′pz}; R, R′ = H (4a); H, CH3, CH6H5 (4c); CH3, C6 H5 (4d) OCH3 (4e); and OC2H5 (4f), respectively. The ligand L is generated in situ through the condensation of 3,5-HRR′pz with acetonitrile under the influence of [(η6-p-cymene)RuCl2]2. The complex [(η6-C6Me6)Ru(μ-Cl)Cl] 2 2 reacts with pyrazole ligands in acetonitrile to yield bis-pyrazole derivatives such as [(η6-C6 Me6)Ru (3,5-HRR′pz)2Cl](BF4) (5a b), where R, R′ = H (5a); H, CH3 (5b) as well as dimeric complexes of pyrazole substituted chloro bridged derivatives [{(η6-C6Me6)Ru(μ-Cl) (3,5-HRR′pz)}2](BF4)2 (5c-g), where R, R′ = CH3 (5c); C6H5 (5d); CH3, C6H5 (5e); OCH3 (5f); and OC2H5 (5g), respectively. These complexes were characterized by FT-IR and FT-NMR spectroscopy as well as analytical data. The molecular structures of representative complexes [(η6-C6Me6)Ru {3(5)-Hmpz}2Cl]+ 5b, [(η6- C6Me6)Ru(μ-Cl)(3,5-Hdmpz)]2 2+ 5c and [(η6-C6Me6) Ru(μ-Cl){3(5)Me,5(3)Ph-Hpz}]22+ 5e were established by single crystal X-ray diffraction studies.
- Govindaswamy,Mozharivskyj, Yurij A.,Kollipara, Mohan Rao
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p. 3265 - 3274
(2007/10/03)
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- Pyrazole-tethered arylphosphine ligands for Suzuki reactions of aryl chlorides: How important is chelation?
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Pyrazole-derived bidentate ligands (P,N-donor) with bulky substituents at the 3-position of the pyrazole, 1b-d, were used with Pd2(dba) 3 to carry out efficient Suzuki coupling reactions with both aryl bromides and chlorides. Enhanced catalytic activity on account of steric crowding in the metal complex suggested participation of a chelated structure in the intermediate catalytic steps.
- Mukherjee, Anuradha,Sarkar, Amitabha
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p. 9525 - 9528
(2007/10/03)
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- The Application of Microreactor Technology for the Synthesis of 1,2-Azoles
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We demonstrate the successful synthesis of an array of 1,2-azoles within a borosilicate glass microreactor whereby conversions in the range of 98-100% were obtained. In terms of large-scale production, this corresponds to 0.339 g day-1 per microreactor when employing reagent concentrations of 1.0 M.
- Wiles, Charlotte,Watts, Paul,Haswell, Stephen J.,Pombo-Villar, Esteban
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- Reactions of tosylhydrazones of benzaldehyde and benzophenone with cyanoalkenes in a basic two-phase system
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Reaction of tosylhydrazones 1a,b with cyanoalkenes 3a,b, carried out in the presence of concentrated aq. sodium hydroxide in dioxane, afforded either cyanocyclopropanes 5, 9 or pyrazoles 13, 14 and 16, 17. The process takes place via generation of diazocompounds 2a,b from 1a,b their [3+2] cycloaddition to 3a,b with the formation of unstable pyrazolines 4, further fate of which depends on the structure of R1 and R2 substituents.
- Jończyk,Wlostowska,Ma?akosza
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p. 2827 - 2832
(2007/10/03)
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- Radical scavenging by N-aminoazaaromatics
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N-Aminoazaaromatics were found to react with nitric oxide in the presence of oxygen to afford deaminated products in high yields. The reaction proceeded almost instantaneously in various solvents including water, and one to two equivalent of NO was consumed depending upon the amount of oxygen coexisted, and 1 equivalent of N2O was released in the reaction. In addition, N-aminoazoles were deaminated by potassium superoxide to give parent azoles in good yields. Two equivalents of superoxide was consumed, and about half equivalents of both nitrite and nitrate ion were released. The results demonstrated that N-aminoazoles have ability to protect the biological system against the oxidation promoted by radicals such as nitrogen oxides and superoxide. Copyright (C) 2000 Elsevier Science Ltd.
- Itoh, Takashi,Miyazaki, Michiko,Maeta, Hiromi,Matsuya, Yuji,Nagata, Kazuhiro,Ohsawa, Akio
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p. 1983 - 1989
(2007/10/03)
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- Reactivity of p-Phenyl Substituted β-Enamino Compounds using K-10/ultrasound. I. Synthesis of Pyrazoles and Pyrazolinones
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The reactivity of the β-enamino ketones, 3-amino-l-(p-phenyl-substituted)-2-buten-l-ones la-d and β-enamino esters. Ethyl-3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d were evaluated by systematic studies of the reactions with hydrazine and methylhydrazine by reactions with solid support K-10/ultrasound and homogeneous media (reflux in ethanol or dichloromethane) yielding pyrazole rings 2a-d, Af-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c. The regiochemistry of the cyclization showed dependence of the reaction conditions employed as well as the substituent in the aromatic ring.
- Valduga, Claudete J.,Braibante, Hugo S.,Braibante, Mara E.F.
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p. 189 - 192
(2007/10/03)
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- Reactivity of p-phenyl substituted β-enamino compounds using K- 10/ultrasound. I. Synthesis of pyrazoles and pyrazolinones
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The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl- substituted)-2-buten-1-ones 1a-d and β-enamino esters, ethyl 3-amino-3-(p- phenyl-substituted)-2-propenoates 5a-d was systematically studied when allowed to react with hydrazine and methylhydrazine under solid support K- 10/ultrasound conditions and in homogeneous media (reflux in ethanol or dichloromethane). The products were pyrazoles 2a-d, N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c. The regiochemistry of the cyclization reactions showed dependence upon the reaction conditions employed as well as upon the substituent in the aromatic ring.
- Valduga,Braibante,Braibante
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p. 1453 - 1457
(2007/10/03)
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- ORGANIC REACTIONS IN THE AQUEOUS MEDIUM Part VI. Synthesis of Substituted Pyrazoles and Pyrazolones
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The reactions of semicarbazide hydrochloride and hydrazine monohydrate with ethyl acetoacetate, acetylacetone, benzoylacetone and dibenzoylmethane leading to the formation of pyrazole and pyrazolone derivatives have been intensively studied in the aqueous as well as in the nonaqueous medium under various sets of conditions. This has resulted in the development of simple and convenient methods for the synthesis of pure ethyl acetoacetate semicarbazone (I), 3-methylpyrazol-5-one-1-carboxamide (II), 3-methylpyrazol-5-one (III), 3,5-dimethylpyrazol-1-carboxamide (V), 3,5-dimethylpyrazole (VI), 3-phenyl-5-methylpyrazole-1-carboxamide (VII), 3-phenyl-5-methylpyrazole (VIII) and 3,5-diphenylpyrazole (IX). It has been suggested that the reaction of semicarbazide hydrochloride with β-diketo compounds proceeds through four stages. A reaction scheme has been proposed to explain the formation of different products. Key words.Synthesis, Pyrazole and Pyrazolone derivatives.
- Ali, Sh. Shaukat,Ashraf, C. M.,Younas, M.,Ehsan, A.
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p. 502 - 510
(2007/10/02)
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- Reactions of N-Aminopyrazoles with Halogenating Reagents and Synthesis of 1,2,3-Triazines
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Reactions of N-aminopyrazoles with halogenating reagents (Cl2, Br2, I2, BrCl, ICl, IBr, N-chlorosuccinimide, and N-bromosuccinimide) were examined.Some of these reagents preferentially lead to oxidation of the amino group to give the corresponding 1,2,3-triazines as major products, while others mainly gave either or both of 1-amino-4-halopyrazoles and 5-halo-1,2,3-triazines as the result of halogenation of the 4-position of the pyrazole ring prior to the oxidation of the amino group.In some cases, the oxidation of the amino group and the halogenation of the pyrazole ring proceeded concurrently to form not only the unhalogenated triazines but also the 1-amino-4-halopyrazoles and the 5-halotriazines.Various reagents and reaction conditions were explored to utilize the reaction for the synthesis of halogenated and unhalogenated 1,2,3-triazines.Keywords - 1,2,3-triazine; halo-1,2,3-triazine; pyrazole; 1-aminopyrazole; 1-aminohalopyrazole; synthesis; oxidation; halogenation; ring expansion
- Ohsawa, Akio,Kaihoh, Terumitsu,Itoh, Takashi,Okada, Mamiko,Kawabata, Chikako,et al.
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p. 3838 - 3848
(2007/10/02)
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- Pyrrole and Pyrazole Ring Closure in Heterogeneous Media
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Pyrroles and pyrazoles may be conveniently prepared by dispersing primary amines or hydrazines and 1,4- or 1,3-diketones, respectively, on alumina or clay (montmorillonite K 10) without solvent, keeping the mixture at 20 deg C or higher temperatures for 1-26 h, and then eluting the product with dichloromethane.
- Texier-Boullet, F.,Klein, B.,Hamelin, J.
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p. 409 - 411
(2007/10/02)
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- Regiospecific synthesis of pyrazoles from 1-azabutadiene derivatives.
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Reaction of 4-amino-1-azabutadienes with different hydrazines leads to pyrazoles.On the other hand, when 4-alkylidene-1-hydrazino-1-azabutadiene derivatives are treated with trifluoroacetic acid, N-alkenylpyrazoles are obtained.
- a Jose,Gotor, Vicente
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p. 1478 - 1492
(2007/10/02)
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- INVESTIGATION OF THE MECHANISMS OF FORMATION OF HETEROCYCLES BY NMR SPECTROSCOPY. III. THE EFFECT OF ELECTRONIC FACTORS ON THE KINETICS OF THE DEHYDRATION OF DIHYDROXYPYRAZOLIDINES AND HYDROXYPYRAZOLINES- THE INTERMEDIATES IN THE REACTION OF HYDRAZINE WITH 1,3-DIKETONES
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The rate constants for the dehydration of the dihydroxypyrazolidine and hydroxypyrazoline intermediates in the reaction of hydrazine with substituted benzoylacetones p-XC6H4COCH2COCH3 (X= CH3O, CH3, H, Cl, NO2) in methanol were determined by NMR spectroscopy using the stopped-flow technique.Increase in the electronegativity of the substituent leads, on the one hand, to an increase in the contribution from the reaction path involving the formation of the tautomeric pyrazoles with the participation of 3-methyl-5-(p-XC6H4)-5-hydroxypyrazoline and, on the other hand, to an increase in the rate of its conversion into the corresponding pyrazole.Analysis of the relationships between the dehydration rates and the Hammett ? constants confirms a reaction mechanism with the participation of the cyclic dihydroxypyrazolidine intermediate.
- Selivanov, S. I.,Golodova, K. G.,Abbasov, Ya. A.,Ershov, B. A.
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p. 1361 - 1364
(2007/10/02)
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- Synthesis of Hydrazone Derivatives by Reaction of Azines with Nitriles, and Their Transformation into Pyrazoles and Pyrimidones
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Reaction of equimolar amount of saturated nitriles and azines affords hydrazone derivatives; with unsymmetrical azines the reaction is regioselective and takes place with an alkyl substituent at the end of the azines opposite to an aryl substituent.Acid catalysed cyclisation and hydrolysis of the hydrazone derivatives yields N-unsubstituted pyrazoles, whereas aluminium chloride catalysed cyclisation of the N-ethoxycarbonyl analogues affords pyrimidones.
- a Jose,Gotor, Vicente
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p. 611 - 614
(2007/10/02)
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- Studies on Paraionic Compounds. Anhydro-1-hydroxy-3-oxopyrazolopyrazolium Hydroxides. Formation and Stability of a Novel Series of 4n? Heterocyclic Betaines.
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Different substituted anhydro-1-hydroxy-3-oxopyrazolopyrazolium hydroxides were prepared by the reaction of 1,3-dicarbonyl compounds with derivatives of 4-phenyl-3,5-dihydroxypyrazole.These diazapentalene derivatives belong to new series of 4n? cyclic betaines which are named "paraionic" heterocycles.The effects of substituents on the stability of both the anionic and the cationic rings were kinetically studied.Selective cleavage of either the anionic or the cationic ring was achieved by varying the conditions of the reaction with morpholine.Electron releasing groups on the cationic ring and electron attracting groups on the anionic ring enhance the stability of the bicyclic system.They also cause a hypsochromic shift of the visible light absorption.
- Zvilichovsky, Gury,David, Mordechai
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p. 295 - 300
(2007/10/02)
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