Amino-Pyrazoles in Medicinal Chemistry: A Review

Lusardi, Matteo; Spallarossa, Andrea; Brullo, Chiara

doi:10.3390/ijms24097834

Cited by 34 publications

(10 citation statements)

References 96 publications

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“…26a Aminopyrazoles are even more important and show a variety of medicinal applications. 26b For instance, they are ligands for receptors or enzymes, such as p38MAPK, and different kinases, such as COX and others. In addition, they possess antibacterial and antiviral activity.…”

Section: Reactions Of Simple Nitro-substituted Heterocyclesmentioning

confidence: 99%

Adventures in the Chemistry of Nitro Compounds

Langer

2024

Synlett

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The present article provides an overview of our work related to cyclization reactions of nitro-substituted electrophilic building blocks with various nucleophiles. As electrophiles, we used nitro-substituted benzoylacetones, 3-ethoxy-2-nitro-2-en-1-ones, 2-nitrobenzoyl chlorides, 4-chloro-3-nitrocoumarin, 2-nitromalonic aldehyde, 3-nitrochromone and 1-(2-chloro-5-nitrophenyl)prop-2-yn-1-ones. As nucleophiles, 1,3-dicarbonyl compounds, 1,3-bis(silyloxy)-1,3-butadienes, (heterocyclic) enamines, hydroxylamine, hydrazines, amines and amino esters were employed. The products include a variety of nitro-substituted carbo- and heterocycles that are not readily available by other methods. The electron-withdrawing nitro group can be easily transformed into an electron-donating amino group which is not only pharmacologically relevant, but can also act as a nucleophile in inter- and intramolecular reactions with electrophiles, such as aldehydes, and can be converted into other functional groups. The nitro group has the capacity to activate compounds for regioselective palladium-catalyzed CH-arylation reactions. Inter- and intramolecular CH arylations of nitro-substituted heterocyclic building blocks, such as 4-nitropyrazoles, 4-nitroimidazoles, 2-nitroindole and nitro-substituted purine analogues, allow for a convenient diversity-oriented approach to the corresponding arylated products. In addition, the nitro group can act as a leaving group in SNAr reactions. Various fused benzofuro[3,2-b]pyridines were prepared by intramolecular SNAr reactions of 2-(hydroxyphenyl)-3-nitropyridines.1 Introduction2 Cyclizations of 1,3-Bis(silyloxy)-1,3-butadienes3 Cyclizations of Heterocyclic Enamines4 Reactions of Simple Nitro-Substituted Heterocycles5 Hydroamination Reactions of Alkynes6 Miscellaneous7 Conclusions

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Section: Reactions Of Simple Nitro-substituted Heterocyclesmentioning

confidence: 99%

Adventures in the Chemistry of Nitro Compounds

Langer

2024

Synlett

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“…Pyrazole, a five-membered heterocyclic ring, is an important scaffold with diverse pharmacological activities such as anticancer, , antimicrobial, , antimalarial, anti-inflammatory, and other activities. − Particularly, the pyrazole ring also plays a crucial role in the development of chemical fungicides. For example, among the 24 commercial SDHI fungicides, up to 12 commercial SDHI fungicides possess a pyrazole fragment (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani

Luo,

Wu,

Ren

et al. 2024

J. Agric. Food Chem.

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In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC 50 value of 0.039 μg/ mL, which was about 20-fold better than that of boscalid (EC 50 = 0.799 μg/mL) and 4-fold more potent than fluxapyroxad (EC 50 = 0.131 μg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 μg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC 50 = 2.04 μM), which was obviously more potent than those of boscalid (IC 50 = 7.92 μM) and fluxapyroxad (IC 50 = 6.15 μM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.

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“…The pyrazole scaffold represents a privileged substructure in medicinal chemistry research and a number of pyrazole derivatives have been evaluated as effective compounds in different therapeutic areas [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ], including infectious diseases [ 17 , 18 ] and also against MRSA [ 19 ]. In previous studies, pyrazole derivatives I ( Figure 1 ) showed significative antibacterial activity against Gram-positive antibiotic-resistant strains [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

Schito,

Caviglia,

Penco

et al. 2024

Pharmaceuticals

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To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a–o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients.

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Amino-Pyrazoles in Medicinal Chemistry: A Review

Cited by 34 publications

References 96 publications

Adventures in the Chemistry of Nitro Compounds

Adventures in the Chemistry of Nitro Compounds

Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

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