36640-48-9Relevant academic research and scientific papers
Substituted imidazole-pyrazole clubbed scaffolds: Microwave assisted synthesis and examined their in-vitro antimicrobial and antituberculosis effects
Desai, Piyush. S.,Pandya, Keyur M.,Patel, Arpan H.,Patel, Janki J.,Patel, Navin B.
, p. 574 - 582 (2021/07/25)
A series of substituted imidazole-pyrazole fused compounds were designed & fused synthesized by employing Debus-Radziszewski one-pot synthesis reaction. Azoles are an extensive and comparatively new class of synthetic compounds including imidazoles and pyrazoles. The current clinical treatment uses compounds of azole framework. Azoles act by inhibiting ergosterol synthesis pathway (a principal component of the fungal cell wall). In addition, a literature review shows that the compounds that include imidazoles and pyrazoles have significant anti-bacterial and anti-mycobacterial effects. In light of the above findings, a series of compounds with imidazole and pyrazole scaffolds were sketched and developed to examine anti-bacterial, antifungal and anti-mycobacterial activities. The structures of the synthesized compounds were characterized using1HNMR,13CNMR, elemental analysis, and MS spectral data. The target compounds were screened for their in-vitro antimicrobial activity against gram-positive and gram-negative bacterial species by disc diffusion method according to the NCCLS (National Committee for Clinical Laboratory Standards) and anti-mycobacterial activity against the Mycobacterium tuberculosis H37Rv strain. The results revealed that imidazole-pyrazole fused scaffold compounds have potential anti-bacterial, antifungal and anti-mycobacterial activities which can be further optimized to get a lead compound.
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.
Novel pyrazole-clubbed thiophene derivatives via Gewald synthesis as antibacterial and anti-inflammatory agents
Nayak, Soukhyarani G.,Poojary, Boja,Kamat, Vinuta
, (2020/09/09)
The aim of this study was to synthesize newer potent Schiff bases by condensing 2-amino-5-(2,4-dichlorophenyl)thiophene-3-carbonitrile and 1,3-disubstituted-1H-pyrazole-4-carbaldehydes, and to investigate their biological activity. The compounds were synthesized via Gewald synthesis and characterized by spectral data and elemental analyses. They were screened for their in vitro antibacterial and anti-inflammatory activities. The synthesized compounds were also evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using the microplate Alamar Blue assay. Compounds 8b, 8c, 8f, 8g, 8k, 8n, and 8o showed promising antibacterial activity. The interactions between the substituted pyrazoles and bovine protein showed promising anti-inflammatory activity. The experimental results revealed compound 8a as a promising antitubercular agent. Hemolytic assays confirmed that the compounds are nontoxic, with percentage hemolysis ranging from 3.6 to 20.1, at a concentration of 1 mg/ml. The results suggest that the pyrazole ring and the substitution pattern on the heterocyclic moiety have an effect on the bioactivity.
Selective synthesis of functionalized pyrazoles from 5-amino-1H-pyrazole-4-carbaldehydes with sodium nitrite: 5-Amino-4-nitrosopyrazoles and pyrazole-4-carbaldehydes
Hsiao, Rong-Hong,Tseng, Ching-Chun,Xie, Jia-Jun,Tsai, Shuo-En,Uramaru,Lin, Ching-Ya,Chern, Ching-Yuh,Wong, Fung Fuh
supporting information, p. 4561 - 4569 (2019/07/10)
A novel and efficient redox reaction was developed to react 5-amino-1H-pyrazole-4-carbaldehyde with sodium nitrite (NaNO2) in an acidic solution (HCl/MeOH) to generate 5-amino-4-nitrosopyrazole, pyrazole-4-carbaldehyde, or diazenylpyrazole selectively. The results showed that 5-amino-4-nitrosopyrazoles were formed as the major product in the diluted acidic solution (≤2 N HCl in MeOH solution) through redox, formylation, and nitrosation reactions of NaNO2. Intriguingly, pyrazole-4-carbaldehyde was the main product under 6 N HCl in MeOH solution.
Design, synthesis, and discovery of 5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and related derivatives as novel inhibitors of mPGES-1
Ding, Kai,Zhou, Ziyuan,Zhou, Shuo,Yuan, Yaxia,Kim, Kyungbo,Zhang, Ting,Zheng, Xirong,Zheng, Fang,Zhan, Chang-Guo
, p. 858 - 862 (2018/02/21)
Human mPGES-1 has emerged as a promising target in exploring a next generation of anti-inflammatory drugs, as selective mPGES-1 inhibitors are expected to discriminatively suppress the production of induced PGE2 without blocking the normal biosynthesis of other prostanoids including homeostatic PGE2. Therefore, this therapeutic approach is believed to reduce the adverse effects associated with the application of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs). Identified from structure-based virtue screening, the compound with (Z)-5-benzylidene-2-iminothiazolidin-4-one scaffold was used as lead in rational design of novel inhibitors. Besides, we further designed, synthesized, and evaluated 5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and structurally related derivatives for their in vitro inhibitory activities. According to in vitro activity assays, a number of these compounds were capable of inhibiting human mPGES-1, with the desirable selectivity for mPGES-1 over COX isozymes.
Antitubercular Activity and Synergistic Study of Novel Pyrazole Derivatives
Jadhav, Sunil B.,Fatema, Samreen,Sanap, Gajanan,Farooqui, Mazahar
, p. 1634 - 1644 (2018/07/24)
A series of 20 novel pyrazole derivatives were designed and prepared, characterized by 1H-NMR, mass spectra (ES-MS), 13C-NMR, and elemental analysis. The synthesized compounds were then evaluated for their growth inhibitory activity
Thiazolo[3,2-a] Pyrimidones as a Novel Anti-TB Agents
Jadhav, Sunil B.,Fatema, Samreen,Bhagat, Sunil S.,Farooqui, Mazahar
, p. 2893 - 2900 (2018/10/24)
A series of novel thiazolo pyrimidine derivatives were designed, synthesized, and assessed for their in vitro anti-mycobacterial activities. All hybrids displayed considerable antitubercular activities against primary Mycobacterium smegmatis mc2 155 screening and successive Mycobacterium tuberculosis H37Rv. In particular, the hybrid entities 13 and 14 (minimum inhibitory concentration: 47 and 39?μg/mL) were found to be equipotent candidates with first-line antitubercular agent rifampicin, which could act as a lead for further optimization.
Discovery of novel double pyrazole Schiff base derivatives as anti-tobacco mosaic virus (TMV) agents
Lv, Xian-Hai,Ren, Zi-Li,Li, Dong-Dong,Ruan, Ban-Feng,Li, Qing-Shan,Chu, Ming-Jie,Ai, Cheng-Ying,Liu, Dao-Hong,Mo, Kai,Cao, Hai-Qun
, p. 377 - 382 (2017/01/28)
Many pyrazole derivatives were reported to exhibit highly activity towards tobacco mosaic virus (TMV). In this work, an optimized pyrazole Schiff base scaffold was designed and introduced to derive novel potential TMV inhibitors. Thirty-six compounds were synthesized, characterized by elemental analysis, mass spectra and nuclear magnetic resonance (NMR) spectroscopy and evaluated by biological experiments. The bioassay results showed that some of the synthesized compounds exhibited excellent anti-TMV activities. Especially, 5-chloro-3-methyl-1H-pyrazole contained compound 4j showed ningnanmycin comparable inhibitory activity and can be considered as potential anti-TMV candidate agent. With molecular docking, compound 4j insert into nucleotide sequence (GAAGUU) of OriRNA stably which revealed nucleotide could be a target of these compounds.
Synthesis, pharmacological activities and molecular docking studies of pyrazolyltriazoles as anti-bacterial and anti-inflammatory agents
Dayakar, Cherupally,Kumar, Buddana Sudheer,Sneha, Galande,Sagarika, Gudem,Meghana, Koneru,Ramakrishna, Sistla,Prakasham, Reddy Shetty,China Raju, Bhimapaka
, p. 5678 - 5691 (2017/10/09)
A series of novel pyrazolyl alcohols (5a-h), pyrazolyl azides (6a-h), and pyrazolyltriazoles (8a-h, 10a-p and 12a-l) were prepared and evaluated for their bioactivity (anti-bacterial and anti-inflammatory) profile. The compound 5c displayed the potent anti-bacterial activity against Micrococcus luteus (MIC 3.9 and MBC 7.81 μg/mL). In vitro anti-inflammatory activity data denoted that compound 8b is effective among the tested compounds against IL-6 (IC50 6.23 μM). Docking analysis of compounds 5f, 8a-b, 8e-f and 8h displayed high binding energies for the compounds 8a-b and 8h towards TNF-α dimer (2AZ5 protein) and IL-6 (1ALU protein). In vivo anti-inflammatory activity of compounds 8b and 8h with respect to LPS induced mice model indicated that compound 8h showed significant reduction in TNF-α.
Design, synthesis, characterization of some new 1,2,3-triazolyl chalcone derivatives as potential anti-microbial, anti-oxidant and anti-cancer agents via a Claisen-Schmidt reaction approach
Bhat, Manjunatha,Nagaraja,Divyaraj,Harikrishna,Sreedhara Ranganath Pai,Biswas, Subhankar,Peethamber
, p. 99794 - 99808 (2016/11/06)
The synthesis of a new series of (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-aryl prop-2-en-1-one (5a-k) and (2E)-1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}-3-(1,3-diaryl-1H-pyrazol-4-yl)prop-2-en-1-one (6a-e) were carried out via a Claisen-Schmidt condensation of 1-{1-[2,3-dichloro-6-methyl-5-(trifluoromethyl)phenyl]-5-methyl-1H-1,2,3-triazol-4-yl}ethanone (4) with different aryl and 1,3-diaryl-1H-pyrazole-4-carbaldehydes iii(a-e) in the presence of ethanol and aqueous sodium hydroxide mixture respectively. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. Further, they were screened for their in vitro anti-microbial, anti-oxidant and anti-cancer activities. Most of the synthesized compounds were displayed broad spectrum of anti-microbial, anti-oxidant activities and some of them exhibits moderate to excellent anti-cancer activities on breast cancer cell lines. Overall, this work has contributed to the development of promising leads for anti-microbial, anti-oxidant and anti-cancer activities.
