- Synthesis of pyrazole-carboxamides and pyrazole-carboxylic acids derivatives: Simple methods to access powerful building blocks
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Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.
- Dos Santos, Maurício Silva,Ferreira, Byanca Silva,Silva, Rafaela Corrêa,Souto, Bernardo Araújo
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p. 335 - 343
(2021/09/07)
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- Novel Pyrazolo[3,4- d]pyrimidin-4-one Derivatives as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation
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Plant pathogenic fungi seriously threaten agricultural production. There is an urgent need to develop novel fungicides with low toxicity and high efficiency. In this study, we designed and synthesized 44 pyrazolo[3,4-d]pyrimidin-4-one derivatives and evaluated them for their fungicidal activities. The bioassay data revealed that most of the target compounds possessed moderate to high in vitro antifungal activities. Especially compound g22 exhibited remarkable antifungal activity against Sclerotinia sclerotiorum with an EC50 value of 1.25 mg/L, close to that of commercial fungicide boscalid (EC50 = 0.96 mg/L) and fluopyram (EC50 = 1.91 mg/L). Moreover, compound g22 possessed prominent protective activity against S. sclerotiorum in vivo for 24 h (95.23%) and 48 h (93.78%), comparable to positive control boscalid (24 h (96.63%); 48 h (93.23%)). Subsequent studies indicated that compound g22 may impede the growth and reproduction of S. sclerotiorum by affecting the morphology of mycelium, destroying cell membrane integrity, and increasing cell membrane permeability. In addition, the application of compound g22 did not injure the growth or reproduction of Italian bees. This study revealed that compound g22 is expected to be developed for efficient and safe agricultural fungicides.
- Cheng, Xiang,Wang, Wei,Wang, Yunxiao,Xia, Dongguo,Yin, Fang,Liu, Qiaoyun,Luo, Huisheng,Li, Meng,Zhang, Chengqi,Cao, Haiqun,Lv, Xianhai
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p. 11395 - 11405
(2021/10/01)
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- Selective targeting of the αC and DFG-out pocket in p38 MAPK
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The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we have explored the highly dynamic back pocket of p38 MAPK with allosteric urea fragments. However, screening against known off-targets showed that these fragments maintained the selectivity issues of their parent compound BIRB-796, while combination with the hinge-binding motif of VPC-00628 greatly enhanced inhibitor selectivity. Further efforts focused therefore on the exploration of the αC-out pocket of p38 MAPK, yielding compound 137 as a highly selective type-II inhibitor. Even though 137 is structurally related to a recent p38 type-II chemical probe, SR-318, the data presented here provide valuable insights into back-pocket interactions that are not addressed in SR-318 and it provides an alternative chemical tool with good cellular activity targeting also the p38 back pocket.
- R?hm, Sandra,Schr?der, Martin,Dwyer, Jessica E.,Widdowson, Caroline S.,Chaikuad, Apirat,Berger, Benedict-Tilman,Joerger, Andreas C.,Kr?mer, Andreas,Harbig, Jule,Dauch, Daniel,Kudolo, Mark,Laufer, Stefan,Bagley, Mark C.,Knapp, Stefan
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- Discovery of novel multi-substituted benzo-indole pyrazole schiff base derivatives with antibacterial activity targeting DNA gyrase
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The design and synthesis of novel multi-substituted benzo-indole pyrazole Schiff base derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activities against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella. In addition, we selected 20 compounds for the in vitro antibacterial activities assay of 6 drug-resistant bacteria strains. The result revealed compound 8I-w exhibited excellent antibacterial activity against 4 drug-resistant E. coli bacteria strains with IC50 values of 7.0, 17.0, 13.5, and 1.0 μM, respectively. In vitro enzyme inhibitory assay showed that compound 8I-w displayed potent inhibition against DNA gyrase with IC50 values of 0.10 μM. The molecular docking model indicated that compounds 8I-w can bind well to the DNA gyrase by interacting with various amino acid residues. This study demonstrated that the compound 8I-w can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.
- Cao, Hai-Qun,Chu, Zhi-Wen,Liu, Hao,Lv, Xian-Hai,Xia, Dong-Guo
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- Pyrazolo pyrimidine derivative and its preparation method and application (by machine translation)
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The invention discloses a pyrazolo pyrimidine ketone derivatives, wherein R1 For nicotinic acid, isonicotinic acid, 2 - chloro nicotinic acid, 6 - chloro nicotinic acid, 2 - bromo nicotinic acid, 6 - bromo nicotinic acid, 2 - fluoro nicotinic acid, 6 - fluoro nicotinic acid, 6 - methoxy nicotinic acid or 2 - methoxy nicotinic acid; R2 Hydrogen, fluoro, chloro or methyl; R3 Is hydrogen or methyl. Also disclosed the preparation method of the derivative and application, by chemical synthetic way to synthesize 40 for the purpose of the compound, and further by the introduction of the the purpose of the chiral compound to the secondary structure is optimized, so that the preparation of the pyrazole and pyrimidinone derivatives with broad-spectrum of cooperativity antifungal activity, in particular to the apple rot bacteria and germ inhibiting activity represent significant; the application in order to develop pyrazolo pyrimidine compound derivatives as the active ingredient to provide the basis for a novel bactericide. (by machine translation)
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Paragraph 0042; 0043; 0044; 0047
(2019/10/23)
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- Novel coumarin-pyrazole carboxamide derivatives as potential topoisomerase II inhibitors: Design, synthesis and antibacterial activity
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The identification of novel Topoisomerase II (Topo II) inhibitors is one of the most attractive directions in the field of bactericide research and development. In our ongoing efforts to pursue the class of inhibitors, six series of 70 novel coumarin-pyrazole carboxamide derivatives were designed and synthesized. As a result of the evaluation against four destructive bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8III-k (MIC = 0.25 mg/L) showed considerable inhibitory activity than ciprofloxacin (MIC = 0.5 mg/L) against Escherichia coli and 8V-c (MIC = 0.05 mg/L) exhibited excellent antibacterial activity than ciprofloxacin (MIC = 0.25 mg/L) against Salmonella. The selected compounds (8III-k, 8V-c and 8V-k) exhibit potent inhibition against Topo II and Topo IV with IC50 values (9.4–25 mg/L). Molecular docking model showed that the compounds 8V-c and 8V-k can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial Topo II inhibiting bactericides.
- Liu, Hao,Ren, Zi-Li,Wang, Wei,Gong, Jie-Xiu,Chu, Ming-Jie,Ma, Quan-Wei,Wang, Jie-Chun,Lv, Xian-Hai
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- Thermal Ring-Opening of Pyrazolo[3,4-d][1,2,3]triazin-4-ones: An Experimental and Theoretical Study
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Several 3-pyrazolylcarbonyl-pyrazolo[3,4-d][1,2,3]triazin-4-ones have been prepared from 5-amino-1H-pyrazole-4-carbonitriles through a simple sequence. In the first step, diazotization of the corresponding aminopyrazoles afforded pyrazolo[3,4-d][1,2,3]triazin-4-ones. Next, thermal rearrangement of these compounds through nitrogen elimination gave the final products. The proposed mechanism for the ring-opening of the pyrazolotriazinones to give the pyrazolylcarbonyl-pyrazolotriazinones involves the generation of an iminoketene intermediate, which reacts with a second molecule of pyrazolotriazinone. The complete mechanism of product formation involving the iminoketene intermediate, and all other reasonable pathways, have been explored in detail through DFT calculations. Furthermore, additional experiments to corroborate the presence of the iminoketene intermediate were carried out.
- Colomer, Juan P.,Sciú, María L.,Ramirez, Cristina L.,Soria-Castro, Silvia M.,Vera, D. Mariano A.,Moyano, Elizabeth L.
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p. 1514 - 1524
(2018/03/30)
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- NOVEL COMPOUNDS FOR USE IN TREATING OR PREVENTING CANCEROUS DISEASES
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The invention relates to new compounds of formula (I) that are useful in medicine, specifically in treating or preventing cancerous diseases in a mammal, to pharmaceutical compositions comprising such compounds, optionally together with other pharmaceutic
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Paragraph 00122
(2017/01/26)
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- Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes
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We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats.
- Sagar, Sneha R.,Agarwal, Jessica K.,Pandya, Dhaivat H.,Dash, Ranjeet Prasad,Nivsarkar, Manish,Vasu, Kamala K.
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supporting information
p. 4428 - 4433
(2015/10/12)
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- 5-Amino-pyrazoles as potent and selective p38α inhibitors
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The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2j was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38α is also disclosed.
- Das, Jagabandhu,Moquin, Robert V.,Dyckman, Alaric J.,Li, Tianle,Pitt, Sidney,Zhang, Rosemary,Shen, Ding Ren,McIntyre, Kim W.,Gillooly, Kathleen,Doweyko, Arthur M.,Newitt, John A.,Sack, John S.,Zhang, Hongjian,Kiefer, Susan E.,Kish, Kevin,McKinnon, Murray,Barrish, Joel C.,Dodd, John H.,Schieven, Gary L.,Leftheris, Katerina
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scheme or table
p. 6886 - 6889
(2011/02/22)
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- Synthesis of some pyrazolopyrimidines
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Some 1-phenyl-1H-6-(un)substituted-5-substituted-arylpyrazolopyrimidine-4(5H)-ones are synthesized by transformation of 6-methyl-1-phenyl-1H-pyrazolooxazin-4-ones and also from 5-amino-4-carbethoxy-1-phenyl pyrazole.
- Pathak, U. S.,Gandhi, Sudha,Rathod, I. S.
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p. 734 - 737
(2007/10/02)
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- Aminopyrazoles. IV. Pyrazol-3- and 5-amines from 2,3-dihaloalkanenitriles or 3-Chloroacrylonitriles and Hydrazines
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2,3-Dihalopropanenitriles and substituted 3-chloropropenenitriles react with hydrazines in basic solution to form either pyrazol-3-amines 4 or pyrazol-5-amines 5 or a mixture of both isomers.
- Ege, Guenter,Franz, Hermann
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p. 1267 - 1273
(2007/10/02)
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