- One-pot synthesis of 3(5)-ethoxycarbonylpyrazoles
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A one-pot synthesis of ethoxycarbonylpyrazoles 2a-e, by the cyclocondensation of β-alkoxyvinyl trichloromethyl ketones 1a-e with hydrazine hydrochloride under mild conditions, is reported. A study using compounds 1a-e with different substituents proved that these are versatile building blocks for the synthesis of pyrazole derivatives, having a 3(5)-ethoxycarbonyl substituent, in good yields (70-91%).
- Martins,Freitag,Flores,Zanatta
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- Pyrazole-oxadiazole conjugates: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
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A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates are comprised of pyrazole and oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. The Type I class has a trimethoxy substituent and the type II class has a 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates, 11a, 11d and 11f manifest potent cytotoxicity with IC50values ranging from 1.5 μM to 11.2 μM and inhibit tubulin polymerization with IC50values of 1.3 μM, 3.9 μM and 2.4 μM respectively. The cell cycle assay showed that treatment with these conjugates results in accumulation of cells in the G2/M phase and disrupts the microtubule network. Elucidation of zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
- Kamal, Ahmed,Shaik, Anver Basha,Polepalli, Sowjanya,Santosh Reddy, Vangala,Bharath Kumar,Gupta, Soma,Rama Krishna,Nagabhushana, Ananthamurthy,Mishra, Rakesh K.,Jain, Nishant
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- Design, synthesis, and preliminary biological evaluation of novel ethyl 1-(2′-hydroxy-3′-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxyla te
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We synthesized a series of novel small molecules, ethyl 1-(2′-hydroxy-3′-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxyla te derivatives 3a-3o, by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 2-aryloxymethylepoxide in the presence of potassium c
- Wei, Fang,Zhao, Bao-Xiang,Huang, Bin,Zhang, Lu,Sun, Chun-Hui,Dong, Wen-Liang,Shin, Dong-Soo,Miao, Jun-Ying
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- Base mediated 1,3-dipolar cycloaddition of α-substituted vinyl phosphonates with diazo compounds for synthesis of 3-pyrazolylphosphonates and 5-pyrazolcarboxylates
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5-Aryl-substituted pyrazol-3-ylphosphonates have been conveniently synthesized by 1,3-dipolar cycloaddition of 1-formamidovinylphosphonates and aryldiazomethanes under K2CO3/MeOH conditions at room temperature. These pyrazoles are formed in one pot via spontaneous elimination of formamide. Basic conditions prevent competitive formation of cyclopropylphosphonates. 3-Aryl substituted pyrazol-5-carboxylates can be synthesized by the same methodology from 1-arylvinylphosphonates and ethyl diazoacetate, although a stronger base NaH is necessary to ensure the success of the aromatization stage with the elimination of the diethoxylphosphoryl moiety.
- Goulioukina, Nataliya S.,Makukhin, Nikolay N.,Shinkarev, Egor D.,Grishin, Yuri K.,Roznyatovsky, Vitaly A.,Beletskaya, Irina P.
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Read Online
- Discovery of Resorcinol-Based Polycyclic Structures as Tyrosinase Inhibitors for Treatment of Parkinson’s Disease
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Tyrosinase is involved in the synthesis of neuromelanin in the substantia nigra, which is closely correlated with the pathogenesis of Parkinson’s disease. Herein, we identified S05014 (l-Tyr, IC50 = 6.25 ± 1.43 nM; l-Dopa, IC50 = 0.6
- Li, Qi,Mo, Jun,Xiong, Baichen,Liao, Qinghong,Chen, Ying,Wang, Yuanyuan,Xing, Shuaishuai,He, Siyu,Lyu, Weiping,Zhang, Ning,Sun, Haopeng
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- A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line
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Abstract: Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160?μM concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure–activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable. Graphic abstract: [Figure not available: see fulltext.].
- Uygun, Meltem Tan,Amudi, Karina,Tura?l?, ?rem Do?an,Menges, Nurettin
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- PIKFYVE KINASE INHIBITORS
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The present invention relates to compounds useful as inhibitors of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) as well as their use for treating diseases and disorders associated with PIKfyve.
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Page/Page column 201; 200
(2021/08/20)
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- Divergent synthesis of 1,3,5-tri and 1,3-disubstituted pyrazoles under transition metal-free conditions
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Pyrazole cores are common structural motifs existing in various agrochemicals and pharmaceuticals. Herein, a transition metal-free, three-component reaction of arylaldehydes, ethyl acrylate and N-tosylhydrazones is described, which leads to the formation of 1,3,5-trisubstituted and 1,3-disubstituted pyrazoles divergently under slightly different conditions. This journal is
- Ma, Liyao,Ou, Pengcheng,Huang, Xueliang
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supporting information
p. 6487 - 6491
(2020/11/10)
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- Pyrazole amide derivatives as well as preparation method and application thereof
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The invention relates to pyrazole derivatives represented by a general formula I shown in the description, or a stereoisomer and tautomer of the pyrazole derivatives, a preparation method of the pyrazole derivatives, and an application of the of the pyraz
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Paragraph 0140; 0144-0146
(2019/05/16)
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- Hydroxamic Acid-Based Histone Deacetylase (HDAC) inhibitors bearing a pyrazole scaffold and a cinnamoyl linker
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Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, recent studies have demonstrated that epigenetic mechanisms are also implicated in the insurgence and development of cancer. Patterns of the epigenetic component in
- Zagni, Chiara,Rescifina, Antonio,Citarella, Andrea,Maugeri, Alessandro,Navarra, Michele,Scala, Angela,Piperno, Anna,Micale, Nicola,Oussama, Mahjoub
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- Fragment-based lead generation of 5-phenyl-1H-pyrazole-3-carboxamide derivatives as leads for potent factor xia inhibitors
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FXIa is suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3-carboxylic acid derivatives as privileged fragments for FXIa inhibitors' lead discovery. After repla
- Wei, Qunchao,Zheng, Zhichao,Zhang, Shijun,Zheng, Xuemin,Meng, Fancui,Yuan, Jing,Xu, Yongnan,Huang, Changjiang
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- Cyclopentene Annulations of Alkene Radical Cations with Vinyl Diazo Species Using Photocatalysis
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A direct (3+2) cycloaddition between alkenes and vinyl diazo reagents using either Cr or Ru photocatalysis is described. The intermediacy of a radical cation species enables a nucleophilic interception by vinyl diazo compounds, a departure from their trad
- Sarabia, Francisco J.,Li, Qiankun,Ferreira, Eric M.
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supporting information
p. 11015 - 11019
(2018/07/30)
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- Synthesis, structure–activity relationships and biological evaluation of 4,5,6,7-tetrahydropyrazolopyrazines as metabotropic glutamate receptor 5 negative allosteric modulators
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The design, synthesis and SAR studies of novel 4,5,6,7-tetrahydropyrazolopyrazines as metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) are presented in this letter. Starting from a HTS hit compound (1, IC50?=?477
- Hirose, Wataru,Kato, Yoshihiro,Yamamoto, Takayoshi,Kassai, Momoe,Takata, Makoto,Hayashi, Shun,Arai, Yukiyo,Imai, Satoki,Yoshida, Kohzo
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p. 3866 - 3869
(2016/08/01)
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- Cascade regioselective synthesis of pyrazoles from nitroallylic acetates and N-tosyl hydrazine
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A simple, practical, and regioselective synthetic protocol for the formation of pyrazoles was developed. Unlike all other previously reported reactions of nitroallylic acetates, this process was initiated by a S N2 reaction at the electrophilic γ site. A plausible mechanism for the cascade SN2-Michael synthesis is proposed.
- Shao, Nana,Chen, Tong,Zhang, Taotao,Zhu, Huajian,Zheng, Qunxiong,Zou, Hongbin
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p. 795 - 799
(2014/01/23)
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- A new class of non-thiazolidinedione, non-carboxylic-acid-based highly selective peroxisome proliferator-activated receptor (PPAR) γ agonists: Design and synthesis of benzylpyrazole acylsulfonamides
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Herein, we describe the design, synthesis, and structure-activity relationships of novel benzylpyrazole acylsulfonamides as non-thiazolidinedione (TZD), non-carboxylic-acid-based peroxisome proliferator-activated receptor (PPAR) γ agonists. Docking model analysis of in-house weak agonist 2 bound to the reported PPARγ ligand binding domain suggested that modification of the carboxylic acid of 2 would help strengthen the interaction of 2 with the TZD pocket and afford non-carboxylic-acid-based agonists. In this study, we used an acylsulfonamide group as the ring-opening analog of TZD as an isosteric replacement of carboxylic acid moiety of 2; further, preliminary modification of the terminal alkyl chain on the sulfonyl group gave the lead compound 3c. Subsequent optimization of the resulting compound gave the potent agonists 25c, 30b, and 30c with high metabolic stability and significant antidiabetic activity. Further, we have described the difference in binding mode of the carboxylic-acid-based agonist 1 and acylsulfonamide 3d.
- Rikimaru, Kentaro,Wakabayashi, Takeshi,Abe, Hidenori,Imoto, Hiroshi,Maekawa, Tsuyoshi,Ujikawa, Osamu,Murase, Katsuhito,Matsuo, Takanori,Matsumoto, Mitsuharu,Nomura, Chisako,Tsuge, Hiroko,Arimura, Naoto,Kawakami, Kazutoshi,Sakamoto, Junichi,Funami, Miyuki,Mol, Clifford D.,Snell, Gyorgy P.,Bragstad, Kenneth A.,Sang, Bi-Ching,Dougan, Douglas R.,Tanaka, Toshimasa,Katayama, Nozomi,Horiguchi, Yoshiaki,Momose, Yu
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experimental part
p. 714 - 733
(2012/03/10)
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- Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4- phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives
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A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5- carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents.
- Nagarapu, Lingaiah,Mateti, Jhansi,Gaikwad, Hanmant K.,Bantu, Rajashaker,Sheeba Rani,Prameela Subhashini
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scheme or table
p. 4138 - 4140
(2011/08/06)
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- Design and synthesis of novel pyrazole-based Lp-PLA2 inhibitors
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A series of novel pyrazole-based lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors have been designed and synthetized by a variety of acetophenones via a 10-step convergent approach. The synthetic approach is carefully opt
- Wang, Yi,Xu, Weiren,Shao, Hua,Xie, Yafei,Wang, Jianwu
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experimental part
p. 2039 - 2048
(2012/03/26)
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- A facile synthesis of pyrazoles with multi-point structural diversity by 1,3-dipolar cycloaddition
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We describe the synthesis of diverse pyrazoles by 1,3-dipolar cycloaddition of ethyl diazoacetate with various acetylenes in refluxing toluene. The product pyrazoles are useful starting points for preparing a diverse collection of trisubstituted pyrazole
- Cheung, Kwai Ming J.,Reynisson, Jóhannes,McDonald, Edward
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supporting information; experimental part
p. 5915 - 5918
(2010/11/18)
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- Parallel synthesis of bis-heterocyclic isoxazolylmethyl- And isoxazolinylmethylpyrazoles
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The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH2-pyrazoles is described, X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloadd
- Meng, Liping,Lorsbach, Beth A.,Sparks, Thomas C.,Fettinger, James C.,Kurth, Mark J.
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experimental part
p. 129 - 136
(2010/10/19)
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- 1,3-Dipolar cycloaddition of diazoacetate compounds to terminal alkynes promoted by Zn(OTf)2: an efficient way to the preparation of pyrazoles
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A series of pyrazoles were prepared in good yields via 1,3-dipolar cycloaddition of diazoacetate compounds to terminal alkynes promoted by Zn(OTf)2 under mild conditions. It was supposed that the reaction was through the intermediate of Zn alky
- He, Sheng,Chen, Li,Niu, Yan-Ning,Wu, Lu-Yong,Liang, Yong-Min
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experimental part
p. 2443 - 2445
(2009/08/07)
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- New one-pot synthesis of pyrazole-5-carboxylates by 1,3-dipole cycloadditions of ethyl diazoacetate with α-methylene carbonyl compounds
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A facile one-pot procedure for the synthesis of pyrazole-5-carboxylates by 1,3-dipolar cycloaddition of ethyl diazoacetate is described. Cycloadditions with α-methylene carbonyl compounds utilizing 1,8-diazabicyclo[5.4.0]undec-7-ene as base and acetonitri
- Gioiello, Antimo,Khamidullina, Asiya,Fulco, Maria Carmela,Venturoni, Francesco,Zlotsky, Simon,Pellicciari, Roberto
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scheme or table
p. 5978 - 5980
(2010/01/18)
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- Copper-promoted cycloaddition of diazocarbonyl compounds and acetylides
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(Chemical Equation Presented) HOMO-logous: The copper-mediated cycloaddition of alkynes with diazo carbonyl compounds to give pyrazoles is reminiscent of the copper-catalyzed cycloaddition of alkynes and azides. The formation of the copper acetylide is proposed to narrow the energy gap between the highest occupied molecular orbital (HOMO) of the alkyne and the lowest unoccupied molecular orbital (LUMO) of the diazo compound.
- Qi, Xiangbing,Ready, Joseph M.
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p. 3242 - 3244
(2008/02/13)
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- Agonist lead identification for the high affinity niacin receptor GPR109a
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A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.
- Gharbaoui, Tawfik,Skinner, Philip J.,Shin, Young-Jun,Averbuj, Claudia,Jung, Jae-Kyu,Johnson, Benjamin R.,Duong, Tracy,Decaire, Marc,Uy, Jane,Cherrier, Martin C.,Webb, Peter J.,Tamura, Susan Y.,Zou, Ning,Rodriguez, Nathalie,Boatman, P. Douglas,Sage, Carleton R.,Lindstrom, Andrew,Xu, Jerry,Schrader, Thomas O.,Smith, Brian M.,Chen, Ruoping,Richman, Jeremy G.,Connolly, Daniel T.,Colletti, Steven L.,Tata, James R.,Semple, Graeme
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p. 4914 - 4919
(2008/02/12)
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- THERAPEUTIC AGENT FOR DIABETES
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The present invention provides an agent for the prophylaxis or treatment of diabetes, which is associated with a ferwer side effects such as body weight gain, adipocyte accumulation, cardiac hypertrophy and the like, and which contains a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
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(2008/06/13)
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- Microwave-assisted synthesis of pyrazoles by 1,3-dipolar cycloaddition of diazo compounds to acetylene derivatives
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Microwave-assisted preparation of a wide range of 5-ethoxycarbonylpyrazoles and 3-pyrazoles by 1,3-dipolar cycloaddition of diazo compound to acetylenes is described. All reactions were carried out using high throughput sequential technique.{A figure is p
- Zrinski, Irena,Juribasic, Marina,Eckert-Maksic, Mirjana
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p. 1961 - 1967
(2007/10/03)
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- Gyrase inhibitors and uses thereof
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The present invention relates to compounds of the formula I: where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacter
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- Nonpeptide endothelin antagonists: From lower affinity pyrazol-5-ols to higher affinity pyrazole-5-carboxylic acids
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Random screening of compounds in endothelin receptor (ET(A) and ET(B)) binding assays led to the discovery of a new class of pyrazol-5-ol ligands. Characterization of structural features crucial for binding activities of these pyrazol-5-ols, by structure-activity-relationship (SAR) studies, allowed us to design a novel class of pyrazole-5-carboxylic acids as more potent ET antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Zhang, Jidong,Didierlaurent, Stanislas,Fortin, Michel,Lefrancois, Dominique,Uridat, Eric,Vevert, Jean Paul
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p. 1351 - 1355
(2007/10/03)
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