77169-12-1Relevant academic research and scientific papers
Novel carboxamide compound and compositions for preventing or treating metabolic diseases comprising the same
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Paragraph 0095-0099; 0150-0151, (2021/09/14)
The present invention relates to a novel carboxamide compound and a composition for preventing or treating metabolic diseases comprising the same, wherein the composition is potent and selective estrogen related receptor (Estrogen-related receptor). ERR)
Urea derivatives of piperazine doped with pyrazole-4-carboxylic acids: Synthesis and antimicrobial evaluation
Devi, Vandana,Phougat, Harshita,Rai, Sanjay,Reddy, T. Shreedhar,Singh, Karan
, (2021/07/06)
A series of novel N-cycloalkyl/aryl-4-(1,3-diphenyl-1H-pyrazole-4-carbonyl)piperazine-1-carboxamides 9a-g has been synthesized for biological interest by simple base catalyzed reaction of various N-cycloalkyl/aryl isocyanates with (1,3-diphenyl-1H-pyrazol
Pd-catalyzed post-Ugi intramolecular cyclization to the synthesis of isoquinolone-pyrazole hybrid pharmacophores & discover their antimicrobial and DFT studies
Pandya, Keyur M.,Battula, Satyanarayana,Naik, Parth J.
supporting information, (2021/09/13)
A novel microwave assisted ligand-free palladium-catalyzed post Ugi reaction for the synthesis of isoquinolone and pyrazole mixed pharmacophore derivatives was achieved from isocyanide and pyrazole substituted amide molecules (synthesized by using Ugi rea
Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B)
Liang, Qianqian,Liu, Hong-Min,Ma, Li-Ying,Ren, Hongmei,Wu, Yang,Zhang, Kun,Zhang, Xinhui,Zhao, Bing,Zheng, Yi-Chao
, (2020/03/10)
KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 μM against KDM5B, and its subsequent optimization to give 1-(4-methoxyphenyl)-N-(2-methyl-2-morpholinopropyl)-3-phenyl-1H-pyrazole-4-carboxamide (27 ab), a potent KDM5B inhibitor with IC50 of 0.0244 μM. In MKN45 cells, compound 27 ab can bind and stabilize KDM5B and induce the accumulation of H3K4me2/3, bona fide substrates of KDM5B, while keep the amount of H3K4me1, H3K9me2/3 and H3K27me2 without change. Further biological study also indicated that compound 27 ab is a potent cellular active KDM5B inhibitor that can inhibit MKN45 cell proliferation, wound healing and migration. In sum, our finding gives a novel structure for the discovery of KDM5B inhibitor and targeting KDM5B may be a new therapeutic strategy for gastric cancer treatment.
Pyrazole-4-carboxylic Acids from Vanadium-catalyzed Chemical Transformation of Pyrazole-4-carbaldehydes
Bala, Renu,Kumari, Poonam,Sood, Sumit,Phougat, Harshita,Kumar, Anil,Singh, Karan
, p. 1787 - 1793 (2019/04/30)
The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole-4-aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H2O2 as an oxidant is described. The catalytic technology was successfully applied to a range of various 4-formylpyrazoles, and plausible mechanism is also discussed.
Substituted 2-phenylpyrazole derivatives and preparation method and application thereof
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Paragraph 0079; 0084, (2019/07/29)
The invention provides substituted 2-phenylpyrazole derivatives and a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The substituted 2-phenylpyrazole derivatives having structures shown as the formul
Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model
Reddy, Velma Ganga,Reddy, T. Srinivasa,Jadala, Chetna,Reddy, M. Soumya,Sultana, Faria,Akunuri, Ravikumar,Bhargava, Suresh K.,Wlodkowic, Donald,Srihari,Kamal, Ahmed
, (2019/08/26)
A series of new pyrazolo-benzothiazole hybrids (7–26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17–6.77 μM, even better than reference drug axitinib (4.88–21.7 μM). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery.
Synthesis of novel 6-(1H-pyrazol-4-yl)-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazoles as potential antimicrobial agents
Pundeer, Rashmi,Ranjan, Pooja,Prakash, Richa,Joshi, Radhika
, p. 92 - 98 (2018/03/05)
Background: Triazolothiadiazoles are molecules of great synthetic and pharmacological significance. They are associated with significant antimicrobial, antifungal, antibacterial, antihelmintic and anti-inflammatory activities. Method: The condensation of 5-alkyl-4-amino-3-mercapto-4H-1, 2, 4-triazoles with 3-aryl-1- phenylpyrazole-4-carboxylic acids was carried out in the presence of phosphoryl chloride and the resulting products were tested in vitro for their antibacterial potential against Bacillus subtilis (gram positive), Staphylococcus aureus (gram positive), Escherichia coli (gram negative) and Pseudomonas aeruginosa (gram negative) and further antifungal properties against Candida albicans, and Saccharomyces cervisiae. Results: A new series of 3-alkyl-6-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1, 2, 4]triazolo[3, 4-b][1, 3, 4] thiadiazoles has been synthesized by the reaction mentioned above. One specific compound, 6-(3-(4- fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-3-methyl-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazole displayed an excellent antifungal activity against Candida albicans with a MIC value of 8 μg/ml, which is actually even better than the standard drug Amphoptericin B (MIC 10 μg/ml). Conclusion: An expeditious synthesis of several new 3-alkyl-6-(3-aryl-1-phenyl-1H-pyrazol-4-yl)- [1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazoles in 77-89 % yield could be performed from readily accessible starting materials, 5-alkyl-4-amino-3-mercapto-4H-1, 2, 4-triazoles and 3-aryl-1-phenylpyrazole-4- carboxylic acids. Most of the resulting compounds showed moderate to good in vitro activity against Gram-positive bacteria. The title compounds seem to be more active against fungi than bacteria.
Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450 CYP121A1: Synthesis and Antimycobacterial Evaluation
Taban, Ismail M.,Elshihawy, Hosam E. A. E.,Torun, Beyza,Zucchini, Benedetta,Williamson, Clare J.,Altuwairigi, Dania,Ngu, Adeline S. T.,McLean, Kirsty J.,Levy, Colin W.,Sood, Sakshi,Marino, Leonardo B.,Munro, Andrew W.,De Carvalho, Luiz Pedro S.,Simons, Claire
, p. 10257 - 10267 (2018/01/10)
Three series of biarylpyrazole imidazole and triazoles are described, which vary in the linker between the biaryl pyrazole and imidazole/triazole group. The imidazole and triazole series with the short -CH2- linker displayed promising antimycobacterial activity, with the imidazole-CH2- series (7) showing low MIC values (6.25-25 μg/mL), which was also influenced by lipophilicity. Extending the linker to -C(O)NH(CH2)2- resulted in a loss of antimycobacterial activity. The binding affinity of the compounds with CYP121A1 was determined by UV-visible optical titrations with KD values of 2.63, 35.6, and 290 μM, respectively, for the tightest binding compounds 7e, 8b, and 13d from their respective series. Both binding affinity assays and docking studies of the CYP121A1 inhibitors suggest type II indirect binding through interstitial water molecules, with key binding residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386, comparable with the binding interactions observed with fluconazole and the natural substrate dicyclotyrosine.
Design, synthesis and biological evaluation of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors
Ganga Reddy,Srinivasa Reddy,Lakshma Nayak,Prasad, Budaganaboyina,Reddy, Adiyala Praveen,Ravikumar,Taj, Shaik,Kamal, Ahmed
, p. 164 - 177 (2016/07/06)
A series of new (N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives (8–35) were designed, synthesized and evaluated as CDK1/Cdc2 inhibitors. Biological evaluation assays indicated that compounds 16 and 27 showed the most potent growth inhibitory activity against human cancer cell lines (MIAPaCa-2, MCF-7 and HeLa) with GI50values ranging from 0.13 to 0.7?μM, compared with the positive control nocodazole (0.81–0.95?μM). Flow cytometric analysis revealed that these compounds induce cell cycle arrest in the G2/M phase and Western blot analysis suggested that compound treatment resulted in reduction of CDK1 expression levels in MCF-7?cell line. Moreover, the apoptosis inducing effect of the compounds was studied using Hoechst staining, Rhodamine 123 staining (MMP), carboxy-DCFDA staining (ROS), Annexin V-FITC assay. Based on these studies, two compounds 16 and 27 have been identified as promising new molecules that have the potential to be developed as leads.
