Showing papers on "Pyrazole published in 2021"
TL;DR: The docking simulation of most active compounds (4g and 4h) were performed within the active site of Aspergillus oryzae α-amylase to analyse the binding conformation and interactions responsible for their activity, and it was found that the binding interactions found between 4g, 4h and α-Amylase were similar to those responsible for α-AMylase inhibition by acarbose.
Abstract: In search of potent α-amylase inhibitors, herein we report the synthesis, molecular docking and QSAR study of some thiazole clubbed pyrazole hybrids (TCPH) i.e., 1-((1-phenyl-3-aryl-1H-pyrazole-4-y...
44 citations
TL;DR: The pyrazole-directed iridium-catalyzed enantioselective borylation of unbiased methylene C-H bonds at the position β to a nitrogen center was reported in this paper.
Abstract: Reported herein is the pyrazole-directed iridium-catalyzed enantioselective borylation of unbiased methylene C-H bonds at the position β to a nitrogen center. The combination of a chiral bidentate boryl ligand, iridium precursor, and pyrazole directing group was responsible for the high regio- and enantioselectivity observed. The method tolerated a vast array of functional groups to afford the corresponding C(sp3 )-H functionalization products with good to excellent enantioselectivity.
38 citations
TL;DR: With this enzymatic system, pyrazole alkylation (methylation, ethylation, propylation) was achieved with unprecedented regioselectivity (>99 %), regiodivergence, and in a first example on preparative scale.
Abstract: Selective alkylation of pyrazoles could solve a challenge in chemistry and streamline synthesis of important molecules. Here we report catalyst-controlled pyrazole alkylation by a cyclic two-enzyme cascade. In this enzymatic system, a promiscuous enzyme uses haloalkanes as precursors to generate non-natural analogs of the common cosubstrate S-adenosyl-l-methionine. A second engineered enzyme transfers the alkyl group in highly selective C-N bond formations to the pyrazole substrate. The cosubstrate is recycled and only used in catalytic amounts. Key is a computational enzyme-library design tool that converted a promiscuous methyltransferase into a small enzyme family of pyrazole-alkylating enzymes in one round of mutagenesis and screening. With this enzymatic system, pyrazole alkylation (methylation, ethylation, propylation) was achieved with unprecedented regioselectivity (>99 %), regiodivergence, and in a first example on preparative scale.
38 citations
TL;DR: A tetratopic bridging ligand 1,1′-(propane-1,3-diyl)bis(1H-pyrazole-3,5-dicarboxylic acid) with functional pyrazole groups was designed and used for reacting with environmentally friendly.
Abstract: A new tetratopic bridging ligand 1,1′-(propane-1,3-diyl)bis(1H-pyrazole-3,5-dicarboxylic acid) (PDC) with functional pyrazole groups was designed and used for reacting with environmentally friendly
37 citations
29 Apr 2021
TL;DR: In this paper, a series of novel indole derivatives linked to the pyrazole moiety were designed and developed via a molecular hybridization protocol as antitumor agents, and the target compounds (5a-j and 7a-e) were screened for their cytotoxicity activities in vitro against four human cancer types.
Abstract: The molecular hybridization concept has recently emerged as a powerful approach in drug discovery. A series of novel indole derivatives linked to the pyrazole moiety were designed and developed via a molecular hybridization protocol as antitumor agents. The target compounds (5a-j and 7a-e) were prepared by the reaction of 5-aminopyrazoles (1a-e) with N-substituted isatin (4a,b) and 1H-indole-3-carbaldehyde (6), respectively. All products were characterized via several analytical and spectroscopic techniques. Compounds (5a-j and 7a-e) were screened for their cytotoxicity activities in vitro against four human cancer types [human colorectal carcinoma (HCT-116), human breast adenocarcinoma (MCF-7), human liver carcinoma (HepG2), and human lung carcinoma (A549)] using the MTT assay. The obtained results showed that the newly synthesized compounds displayed good-to-excellent antitumor activity. For example, 5-((1H-indol-3-yl)methyleneamino)-N-phenyl-3-(phenylamino)-1H-pyrazole-4-carboxamide (7a) and 5-((1H-indol-3-yl)methyleneamino)-3-(phenylamino)-N-(4-methylphenyl)-1H-pyrazole-4-carboxamide (7b) provided excellent anticancer inhibition performance against the HepG2 cancer cell line with IC50 values of 6.1 ± 1.9 and 7.9 ± 1.9 μM, respectively, compared to the standard reference drug, doxorubicin (IC50 = 24.7 ± 3.2 μM). The two powerful anticancer compounds (7a and 7b) were further subjected to cell cycle analysis and apoptosis investigation in HepG2 using flow cytometry. We have also studied the enzymatic assay of these two compounds against some enzymes, namely, caspase-3, Bcl-2, Bax, and CDK-2. Interestingly, the molecular docking study revealed that compounds 7a and 7b could well embed in the active pocket of the CDK-2 enzyme via different interactions. Overall, the prepared pyrazole-indole hybrids (7a and 7b) can be proposed as strong anticancer candidate drugs against various cancer cell lines.
37 citations
TL;DR: In this article, a series of new bis-thiazolyl-pyrazole derivatives 3, 4a-c, 5a, b, and 6a -c was synthesized by reacting bis hydrazonoyl bromide with several active methylene reagents in a one-pot reaction.
34 citations
TL;DR: A series of pyrazole derivatives 4, 5, 6, 12, 13, 14 as well as hydrazone derivatives 7, 10, 11 were synthesized starting from adamantane-1-carbohydrazide as the bioactive core.
33 citations
TL;DR: The development of new 1,3,5-triazine-based pyrazole derivatives as effective anticancer agents and their applications in clinical practice are studied.
Abstract: We herein report the design and synthesis of new 1,3,5-triazine-based pyrazole derivatives (5a–i) with anticancer activity targeting the epidermal growth factor (EGFR) tyrosine kinase. The newly synthesized compounds were characterized using spectroscopic techniques such as 1H NMR, 13C NMR, mass spectrometry and elemental analysis. All the compounds exhibited moderate to good anticancer activity against MCF-7 (human breast), HepG2 (human liver), HCT116 (human colorectal), PC-3 (human prostate), LoVo (human colon) and LoVo/DX (doxorubicin-resistant) cancer cell lines except compound 5i, which exhibited poor activity. Compounds 5f, 5g and 5h possessed more promising anticancer activity and the results were expressed as IC50 values in nM. These compounds also displayed potent inhibitory activity against EGFR-tyrosine kinase with IC50 values of 395.1, 286.9 and 229.4 nM, respectively in comparison with the standard drug, erlotinib. The docking studies revealed that the compounds showed a good affinity towards the target EGFR kinase (PDB ID: 6V6O) by forming multiple H-bonds with amino acids. The binding interaction of the more active compounds (5f, 5g and 5h) with Ct-DNA was explored using spectroscopic, viscometric, electrochemical and docking techniques. Both the experimental and theoretical findings of DNA binding showed consistent results and confirmed the groove mode of interaction of these compounds with DNA. The in vitro ADME properties were also evaluated, thus allowing the identification of optimized compounds as promising anticancer agents. Finally, density functional theory (DFT) geometry optimization and the relevant quantum parameters were calculated for the active compounds using the B3LYP level.
33 citations
TL;DR: A green synthetic route to the convenient preparation of tetrahydrobenzo[b]pyran, pyrano[2,3-d]pyrimidinone and dihydropyrano [2, 3-c]pyrazole scaffolds have been developed using theophylline as a gr...
30 citations
TL;DR: A series of novel pyrazole-phenyl semicarbazone derivatives were designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity and it was suggested that electronic properties of substitutions have little effect on inhibitory potential of compounds.
29 citations
TL;DR: In this article, a novel crystal i.e. (E)-N'-(4-chlorobenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide has been synthesized and characterized using various spectroscopic techniques.
TL;DR: In this article, a series of substituted pyrazole derivatives was designed to ultimately address the phytotoxicity to wheat caused by Fenoxaprop-p-ethyl (FE), a type of acetyl-CoA carboxylase (ACCase) inhibitor.
Abstract: Fenoxaprop-p-ethyl (FE), a type of acetyl-CoA carboxylase (ACCase) inhibitor, has been extensively applied to a variety of crop plants. It can cause damage to wheat (Triticum aestivum) even resulting in the death of the crop. On the prerequisite of not reducing herbicidal efficiency on target weed species, herbicide safeners selectively protect crops from herbicide injury. Based on fragment splicing, a series of novel substituted pyrazole derivatives was designed to ultimately address the phytotoxicity to wheat caused by FE. The title compounds were synthesized in a one-pot way and characterized via infrared spectroscopy, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioactivity assay proved that the FE phytotoxicity to wheat could be reduced by most of the title compounds. The molecular docking model indicated that compound IV-21 prevented fenoxaprop acid (FA) from reaching or acting with ACCase. The absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound IV-21 exhibited superior pharmacokinetic properties to the commercialized safener mefenpyr-diethyl. The current work revealed that a series of newly substituted pyrazole derivatives presented strong herbicide safener activity in wheat. This may serve as a potential candidate structure to contribute to the further protection of wheat from herbicide injury.
TL;DR: In this article, a mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs.
Abstract: Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.
TL;DR: The synthesis of pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid.
Abstract: The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological activities. The synthesis of the pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid. The compounds are obtained in good yields 68–99% and their structure was confirmed using IR, 1H-NMR, 13C-NMR and elemental analysis. The novel derivatives were studied in vitro for their antioxidant, anti-lipid peroxidation (AAPH) activities and inhibitory activity of lipoxygenase. Both classes strongly inhibit lipid peroxidation. Compound 2g was the most potent lipoxygenase inhibitor (IC50 = 80 µM). The inhibition of the carrageenin-induced paw edema (CPE) and nociception was also determined, with compounds 2d and 2e being the most potent. Compound 2e inhibited nociception higher than 2d. Pyrazoline 2d was found to be active in a preliminary test, for the investigation of anti-adjuvant-induced disease (AID) activity. Pyrazoline derivatives were found to be more potent than pyrazoles. Docking studies of the most potent LOX inhibitor 2g highlight hydrophobic interactions with VAL126, PHE143, VAL520 and LYS526 and a halogen bond between the chlorine atom and ARG182.
TL;DR: In this paper, the pyrazole nucleating ligand was used to construct two novel complexes by using FT-IR, NMR and thermal studies, and their structural investigation was performed by elemental analyses, FTIR and NMR.
TL;DR: Hypervalent iodine(iii)-derivatives display higher catalytic activity than other aliphatic and aromatic iodine(i)– or bromine(i)-containing substrates for a Knorr-type reaction of N-acetyl hydrazides with acetyl acetone to give N-acyl pyrazoles.
Abstract: Hypervalent iodine(III)-derivatives display higher catalytic activity than other aliphatic and aromatic iodine(I)– or bromine(I)-containing substrates for a Knorr-type reaction of N-acetyl hydrazides with acetyl acetone to give N-acyl pyrazoles. The highest activity was observed for dibenziodolium triflate, for which 10 mol% resulted in the generation of N-acyl pyrazole from acyl hydrazide and acetyl acetone typically at 50 °C for 3.5–6 h with up to 99% isolated yields. 1H NMR titration data and DFT calculations indicate that the catalytic activity of the iodine(III) is caused by the binding with a ketone.
TL;DR: In this paper, pyrazolo[1,5-a]pyrimidines 14a-j and pyrazole derivatives as Schiff bases 16a−j have been synthesized by the reaction of 5-amino-pyrazole derivative 9a, b with 2-(arylidene)malononitriles 10a-e or various aldehydes 15a−e, respectively.
Abstract: Twenty compounds of pyrazolo[1,5-a]pyrimidines 14a–j and pyrazole derivatives as Schiff bases 16a–j have been synthesized by the reaction of 5-amino-pyrazole derivatives 9a, b with 2-(arylidene)malononitriles 10a–e or various aldehydes 15a–e, respectively. The biological activity of the pyrazolo[1,5-a]pyrimidines 14a–j and pyrazole derivatives 16a–j was evaluated and showed a variation in antimicrobial inhibitory activity. In particular, the three pyrazolo[1,5-a]pyrimidines (14b, 14e, and 14j) and four pyrazole Schiff bases (16c, 16d, 16 h, and 16i) have possessed a broad spectrum of activity with the inhibition zone range from 15 to 20 mm. Also, the structure–activity relationship study was done. Furthermore, physicochemical properties, drug-likeness model score, bioactivity scores, ADME, and toxicity properties were predicted in silico and some products possessed acceptable and a good results. Finally, the molecular docking studies performed inside the active site of DNA gyrase (PDB: 2XCT), the secreted aspartic protease from C. albicans (PDB: 1ZAP), and exhibited lower binding energy with different types of binding mode. Besides, the electrostatic potential maps were generated to determine the charge distribution around a molecule and therefore determine the regions that could form hydrogen bonding donors and acceptors that confirmed the binding mode in the docking study. The results suggested that these derivatives could act as antimicrobial agents.
TL;DR: In this article, a novel hydrazine-functionalized strategy was utilized for the synthesis of pyrazole-based energetic materials, giving rise to a new family of P-fused compounds and N-nitramine compounds with excellent properties.
TL;DR: In this paper, a series of quinazolinone-pyrazole hybrids were designed, synthesized and screened for their α-glucosidase inhibitory activity.
TL;DR: In this article, the diversity-oriented synthesis strategy with α,β-unsaturated carbonyl compounds was taken advantage of the DNA-compatible transformations for various heterocyclic scaffolds.
TL;DR: In this paper, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities.
Abstract: Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds a1-a6, b1-b3, b7, b10, b13, and b18. For the antifungal activity, the minimal EC50 values could afford 0.47 (a2), 1.05 (a2), 0.65 (a1), and 1.32 μg/mL (b3) against the corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, and Rhizoctonia solani. In vivo pot experiments against corn scab (caused by G. z.) revealed that the compound a2 was effective with protective and curative activities of 90.2 and 86.3% at 200 μg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC50 = 3.21 μM, a2) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds b2 and a4 yielded superior anti-oomycete and antibacterial activities toward Phytophora infestins and Xanthomonas oryzae pv. oryzae with EC50 values of 2.92 and 8.43 μg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% (a4) at 200 μg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.
TL;DR: Structural–activity relationship analysis revealed that the presence of 2,4-dichloro moiety surprisingly influenced the activity of the compounds and suggested that compounds 3a and 4b preferably interact with the targets through hydrogen bonding.
Abstract: A library of pyrazole–thiazolidinone conjugates was synthesized using a molecular hybridization approach through a Vilsmeier–Haack reaction. The compounds were tested for anti-microbial activity against two Gram-positive bacteria (Staphylococcus aureus and methicillin-resistant Staphylococcus aureus) and four Gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa). Among the compounds tested, 3-((2,4-dichlorophenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-yl)methylene)hydrazinecarbothioamide (3a) and 2-((3-(2-chlorophenyl)-1-(2,4 dinitrophenyl)-1H-pyrazol-4-yl)methyleneamino)thiazolidin-4-one (4b) emerged as the most potent anti-microbial compounds with minimum bactericidal concentrations of < 0.2 µM against MRSA and S. aureus. Structure–activity relationship analysis further revealed that the presence of 2,4-dichloro moiety surprisingly influenced the activity of the compounds. Molecular docking studies of the compounds into the crystal structure of topoisomerase II and topoisomerase IV suggest that compounds 3a and 4b preferably interact with the targets through hydrogen bonding.
TL;DR: In this article, the reaction of enaminone 3 with some nitrogen nucleophiles to afford the corresponding pyrazole 4, isoxazole 5, and pyrimidine 6 derivatives was studied.
Abstract: We studied the reaction of enaminone 3 with some nitrogen nucleophiles to afford the corresponding pyrazole 4, isoxazole 5, and pyrimidine 6 derivatives, and the reactivity of enaminone 3 with heterocyclic amines to afford the corresponding fused pyrrolo[1,2-a]pyrimidine 9a, imidazo[1,2-a]pyrimidine 9b, phenylpyrrolo[1,2-a]pyrimidine 9c, and benzo[4,5]imidazo[1,2-a]pyrimidine 11 derivatives. Additionally, the electrophilic azo-coupling reaction of enaminone 3 with aromatic diazonium salts in pyridine afforded the corresponding intermediate hydrazines 13a–d, which cyclized to pyrazolo[5,1-c][1,2,4]triazine derivatives 14a–d. Moreover, addition of (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (3) with hydrazonoyl chloride derivatives 15a,b gave novel pyrazole derivatives 17a,b. Almost all of the synthesized heterocyclic compounds exhibited antimicrobial and in vitro anticancer activity (HepG2 and MCF-7 cell lines). Furthermore, the molecular docking of the most effective compound, i.e., 7-(4-fluorophenyl)pyrazolo[5,1-c][1,2,4]triazin-3-yl)(2-hydroxyphenyl)methanone (14c), was studied against (PDB ID: 3t88), (PDB ID: 2wje), (PDB ID: 4ynt), and (PDB ID: 1tgh) to investigate its antimicrobial activity when attached to different proteins with short bond length. Compound 14a docked with (PDB ID: 4hdq) and (PDB ID: 3pxe) with energy affinity of −9.946 and −10.55 kcal/mol, with the pyrazolo[5,1-c][1,2,4]triazine derivative involved in the pockets of the proteins. Moreover; the theoretical and investigational studies of compounds 14a,c were compatible with spectral data obtained at HF/6-31G(d) and DFT/B3LYP/6-31G(d) level.
TL;DR: In this article, Na2 eosin Y-derived photoexcited states functions as a direct hydrogen atom transfer (HAT) catalyst to synthesize dihydropyrano[2,3-c]pyrazole scaffolds photochemically via four-condensation domino reaction of tandem Knoevenagel-Michael cyclocondensation reaction.
Abstract: Evidence indicates that Na2 eosin Y-derived photoexcited states functions as a direct hydrogen atom transfer (HAT) catalyst to synthesize dihydropyrano[2,3-c]pyrazole scaffolds photochemically via four-condensation domino reaction of tandem Knoevenagel-Michael cyclocondensation reaction ethyl acetoacetate, hydrazine hydrate, aryl aldehyde derivatives and malononitrile via visible light-mediated in aqueous ethanol at ambient temperature under air atmosphere. This study paves the new role for further the use of a metal-free organic dye with commercial availability and inexpensiveness, Na2 eosin Y in photochemical synthesis with use of the lowest amount of catalyst, excellent yields, time-saving aspects of the reaction and high atom economy. Notably, this cyclization is also runnable on the gram scale, which highlights the potentiality of using this reaction in industrial uses.
TL;DR: In this article, the authors describe an efficient and efficient method for substituting thiazole-substituted pyrazole with pyrazoles for antiviral, antitubercular, analgesic and anticancer agents.
Abstract: Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient a...
TL;DR: Inspired by commercially established fluxapyroxad as the lead compound of novel efficient antifungal ingredients, novel pyrazole carboxylate derivatives containing a flexible thiazole backbone were successfully designed, synthesized, and detected for their in vitro and in vivo biological activities against eight agricultural fungi as discussed by the authors.
Abstract: Inspired by commercially established fluxapyroxad as the lead compound of novel efficient antifungal ingredients, novel pyrazole carboxylate derivatives containing a flexible thiazole backbone were successfully designed, synthesized, and detected for their in vitro and in vivo biological activities against eight agricultural fungi. The antifungal bioassay results showed that compound 24 revealed excellent bioactivities against Botrytis cinerea and Sclerotinia sclerotiorum, with median effective concentrations (EC50) of 0.40 and 3.54 mg/L, respectively. Compound 15 revealed remarkable antifungal activity against Valsa mali, with an EC50 value of 0.32 mg/L. For in vivo fungicide control against B. cinerea and V. mali, compounds 3 and 24 at 25 mg/L, respectively, displayed prominent efficacy on cherry tomatoes and apple branches. Molecular docking results demonstrated that compound 15 could form an interaction with several crucial residues of succinate dehydrogenase (SDH), and the in vitro enzyme assay indicated that the target compound 15 displayed an inhibitory effect toward SDH, with an IC50 value of 82.26 μM. The experimental results indicated that phenyl pyrazole carboxylate derivatives displayed a weak antifungal property and low activity compared to the other title substituent pyrazole carboxylate derivatives. Compounds 3, 15, and 24 are promising antifungal candidates worthy of further fungicide development due to their prominent effectiveness.
TL;DR: Compounds 6a and 6b (possess SO2NH2 as selective COX-2 pharmacophore) presented the highest anti-inflammatory activity and have the lowest ulcerogenic liability reflecting their expected safe GI profiles.