36640-42-3Relevant articles and documents
Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities
Wang, Wang,Xiong, Liangliang,Li, Yutong,Song, Zhuorui,Sun, Dejuan,Li, Hua,Chen, Lixia
, (2022/01/24)
As our ongoing work on lathyrane diterpenoid derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated t
Design and synthesis of novel pyrazole-phenyl semicarbazone derivatives as potential α-glucosidase inhibitor: Kinetics and molecular dynamics simulation study
Azimi, Fateme,Ghasemi, Jahan B.,Azizian, Homa,Najafi, Mohammad,Faramarzi, Mohammad Ali,Saghaei, Lotfollah,Sadeghi-aliabadi, Hojjat,Larijani, Bagher,Hassanzadeh, Farshid,Mahdavi, Mohammad
, p. 1082 - 1095 (2020/11/20)
A series of novel pyrazole-phenyl semicarbazone derivatives were designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. Given the importance of hydrogen bonding in promoting the α-glucosidase inhibitory activity, pharmacophore modification was established. The docking results rationalized the idea of the design. All newly synthesized compounds exhibited excellent in vitro yeast α-glucosidase inhibition (IC50 values in the range of 65.1–695.0 μM) even much more potent than standard drug acarbose (IC50 = 750.0 μM). Among them, compounds 8o displayed the most potent α-glucosidase inhibitory activity (IC50 = 65.1 ± 0.3 μM). Kinetic study of compound 8o revealed that it inhibited α-glucosidase in a competitive mode (Ki = 87.0 μM). Limited SAR suggested that electronic properties of substitutions have little effect on inhibitory potential of compounds. Cytotoxic studies demonstrated that the active compounds (8o, 8k, 8p, 8l, 8i, and 8a) compounds are also non-cytotoxic. The binding modes of the most potent compounds 8o, 8k, 8p, 8l and 8i was studied through in silico docking studies. Molecular dynamic simulations have been performed in order to explain the dynamic behavior and structural changes of the systems by the calculation of the root mean square deviation (RMSD) and root mean square fluctuation (RMSF).
Design, synthesis and in vitro antitumor evaluation of novel pyrazole-benzimidazole derivatives
Gao, Jin-Ming,Ji, Kegong,Liu, Rong-Chun,Ren, Bo,Tang, Jiang-Jiang
, (2021/06/03)
A series of novel pyrazole-benzimidazole derivatives (6–42) have been designed, synthesized and evaluated for their in vitro antiproliferative activity against the HCT116, MCF-7 and Huh-7 cell lines. Among them, compounds 17, 26 and 35 showed significant
Synthesis, characterization and antibacterial evaluation of 2, 3dihydroquinazolin-4 (1h)-ones and some new bis 2, 3-dihydroquinazolin-4 (1h)-ones using pre-made pyrazole carbaldehyde derivatives
Mahmoodi, Nosrat Ollah,Sina, Kiana Faraji,Yahyazadeh, Asieh
, p. 176 - 182 (2021/03/19)
2, 3-Dihydroquinazolinones are of popular compounds with the diversification of biological and pharmacological activities. Among many discovered methods, there are efficient and convenient methods used for the synthesis of 2, 3-dihydroquinazoline-4 (1H)-one and some new bis 2, 3-dihydroquinazoline-4 (1H)-one derivatives which are reported in this study. The mentioned methods include the two-component condensation of one molecule of anthranilamide and one molecule of pyra-zole carbaldehyde using montmorillonite-K10 as a catalyst for the preparation of 2, 3 dihydroquinazo-line-4 (1H)-ones. Also, one-pot pseudo-five-component reaction (5MCRs) of two molecules of isatoic anhydride, two molecules of pyrazole carbaldehydes and one molecule of ethan-1, 2-diamine in the presence of the r catalyst (montmorillonite-K10) for the synthesis of bis 2, 3-dihydroquinazoline-4 (1H)-ones. Despite the short times of reactions, high yields of products were obtained, which were val-idated using FT-IR,1HNMR,13CNMR, and elemental analysis. Moreover, the compounds were screened for their antimicrobial activities against two-gram-positive bacterial strains: Staphylococcus aureus and Micrococcus Luteus; and against two-gram-negative bacterial strains, as well: Escherichia coli and Pseudomonas aeruginosa, which all were utilized for antibacterial investigations. The results showed moderate or significant antibacterial activities.
Design and synthesis of novel quinazolinone-pyrazole derivatives as potential α-glucosidase inhibitors: Structure-activity relationship, molecular modeling and kinetic study
Azimi, Fateme,Azizian, Homa,Najafi, Mohammad,Hassanzadeh, Farshid,Sadeghi-aliabadi, Hojjat,Ghasemi, Jahan B.,Ali Faramarzi, Mohammad,Mojtabavi, Somayeh,Larijani, Bagher,Saghaei, Lotfollah,Mahdavi, Mohammad
, (2021/07/13)
In this study, a new series of quinazolinone-pyrazole hybrids were designed, synthesized and screened for their α-glucosidase inhibitory activity. The results of the in vitro screening indicated that all the molecular hybrids exhibited more inhibitory activity (IC50 values ranging from 60.5 ± 0.3 μM-186.6 ± 20 μM) in comparison to standard acarbose (IC50 = 750.0 ± 10.0 μM). Limited structure–activity relationship suggested that the variation in the inhibitory activities of the compounds affected by different substitutions on phenyl rings of diphenyl pyrazole moiety. The enzyme kinetic studies of the most potent compound 9i revealed that it inhibited α-glucosidase in a competitive mode with a Ki of 56 μM. Molecular docking study was performed to predict the putative binding interaction. As expected, all pharmacophoric moieties used in the initial structure design playing a pivotal role in the interaction with the binding site of the enzyme. In addition, by performing molecular dynamic investigation and MM-GBSA calculation, we investigated the difference in structural perturbation and dynamic behavior that is observed over α-glycosidase in complex with the most active compound and acarbose relative to unbound α-glycosidase enzyme.
H3PO4 catalyzed one-pot synthesis of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde to novel 1,3-diphenyl-1H-pyrazole-4-carbonitrile
Choudhare, Tukaram S,Netankar, Prashant D,Shirsath, Sagar E,Wagare, Devendra S
, (2021/07/10)
Abstract: One-pot condensation of pyrazole-4-aldehydes and hydroxylamine hydrochloride to form the corresponding oxime using formic acid as a medium and further dehydration of oxime using a catalytic amount of orthophosphoric acid to afford novel pyrazole-4-carbonitrile. This protocol serves as an ortho-phosphoric acid-catalyzed one-pot conversion of aldehyde to nitrile. Most remarkable features of this method are metal-free, cost-effective, atom efficiency with excellent yield (98–99%). This process will serve as a robust and scalable tool for the synthesis of valuable and versatile precursor (nitriles). This precursor will pave the way for the synthesis of various medicinally important valuable compounds. Graphic abstract: [Figure not available: see fulltext.].
PYRAZOLYLACYLPYRAZOLINE COMPOUNDS AND METHOD FOR TREATING PAIN
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Paragraph 0172; 0227, (2021/05/29)
This invention relates to pyrazolylacylpyrazoline compounds or pharmaceutically acceptable salts thereof, and for the use of the compounds to treat neurological disorders.
New library of pyrazole–imidazo[1,2-α]pyridine molecular conjugates: Synthesis, antibacterial activity and molecular docking studies
Ebenezer, Oluwakemi,Awolade, Paul,Koorbanally, Neil,Singh, Parvesh
, p. 162 - 173 (2019/11/03)
A library of novel pyrazole–imidazo[1,2-α]pyridine scaffolds was designed and synthesized through a one-pot three-component tandem reaction. The structures of synthesized conjugates were confirmed by spectroscopic techniques (NMR, IR and HRMS). In vitro antibacterial evaluation of the twelve synthesized molecules (7a, 8a–k) against methicillin-resistant Staphylococcus aureus and normal strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa established 8b, 8d, 8e, 8h and 8i as potent antibacterial agents with superior minimum bactericidal concentration, compared with standard drug ciprofloxacin. Molecular docking studies of all active compounds into the binding site of glucosamine-6-phosphate synthase were further performed in order to have a comprehensive understanding of putative binding modes within the active sites of the receptor.
In vitro studies of potent aldose reductase inhibitors: Synthesis, characterization, biological evaluation and docking analysis of rhodanine-3-hippuric acid derivatives
Celestina, Stephen Kumar,Ravi, Subban,Sundaram, Kaveri
, (2020/02/22)
Inhibitors of aldose reductase are rate-limiting enzymes and could play a key role to prevent the complications of diabetes. In our attempt to develop novel inhibitors of aldose reductase, the derivatives of rhodanine-3-hippuric acid-pyrazole hybrid were synthesized and characterised by spectral data. The biological studies reveal that all the compounds show an excellent activity against ALR2 with IC50 values ranging from 0.04 to 1.36 μM. Among these the synthesised compounds 6a-m, 6g and 6e showed specific inhibitory activity with IC50 values of 0.04 and 0.06 μM respectively against ALR2 and found to be more potent than epalrestat (IC50 = 0.87 μM), the only aldose reductase inhibitor currently used in the therapy. Molecular docking analysis using the AR-NADP+ complex as a receptor was performed with all the synthesized compounds. All the compounds exhibit a well-defined binding mode within the AR active site, similarly to previous described AR inhibitors, with the anion head group bound to the catalytic center, blocking thus its activity. By forming hydrogen bonds with Tyr48 and His110 of the protein from ALR2 (PDB ID: 2FZD), the compounds 6g and 6e interrupt the proton donation mechanism, which is necessary for the catalytic activity of ALR2.
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.
