An Overview of Pyrazole-Tetrazole-Based Hybrid Compounds: Synthesis Methods, Biological Activities and Energetic Properties
Mounir Cherfi, Tarik Harit, Malika Amanchar, Ahlam Oulous, Fouad Malek
Organics · pp. 575–597 · Published 5 Dec 2024
10.3390/org5040030Abstract
Pyrazole and tetrazole are among the most important heterocyclic members of the azole family. Over the past decade, these N-heterocycles and their derivatives have demonstrated specific properties that give them potent applications in several fields such as pharmacology, technology, and agriculture. Combining these two azoles in single hybrid architecture has given rise to highly potent molecules in terms of efficacy and specificity, with enhanced and scalable properties. In this context, the present paper deals with the literature of the last 10 years describing the synthesis protocols for pyrazole-tetrazole-based molecules. Their biological activities as well as their energetic properties are also reported.
References (80)
- 1 Alivisatos, 1980, From molecules to materials: Current trends and future directions [DOI]
- 2 Gupta, R.R., Kumar, M., and Gupta, V. (2013). Heterocyclic Chemistry: Volume II: Five-Membered Heterocycles, Springer Science & Business Media.
- 3 Dorababu, 2020, Pharmacology Profile of Recently Developed Multi-Functional Azoles; SAR-Based Predictive Structural Modification [DOI]
- 4 Umetsu, 2020, Development of novel pesticides in the 21st century [DOI]
- 5 Ghosh, 2022, Visible light-induced functionalization of indazole and pyrazole: A recent update [DOI]
- 6 Petrov, V.A. (2009). Fluorinated Heterocyclic Compounds: Synthesis, Chemistry, and Applications, John Wiley & Sons. [DOI]
- 7 Sadek, 2023, Recent developments in the synthesis of hybrid heterocycles, a promising approach to develop multi-target antibacterial agents [DOI]
- 8 Mahmoud, 2022, Recent progress in biologically active indole hybrids: A mini review [DOI]
- 9 Gattu, R., Ramesh, S.S., Nadigar, S., and Ramesh, S. (2023). Conjugation as a tool in therapeutics: Role of amino acids/peptides-bioactive (including Heterocycles) hybrid molecules in treating infectious diseases. Antibiotics, 12. [DOI]
- 10 Araji, 2024, Cross-over from pyrene to acene optical and electronic properties: A theoretical investigation of a series of pyrene derivatives fused with N-, S, and O-containing heterocycles [DOI]
- 11 Gao, 2020, Fused heterocycle-based energetic materials (2012–2019) [DOI]
- 12 Cherfi, 2023, New macrocycles based on pyrazole-tetrazole subunit: Synthesis, characterization and their complexing properties toward heavy metal cations [DOI]
- 13 Sarkar, 2023, An efficient 2-(2-Pyridyl) imidazole based copper catalyst for N-Arylation of N-heterocycles [DOI]
- 14 Ebenezer, O., Shapi, M., and Tuszynski, J.A. (2022). A review of the recent development in the synthesis and biological evaluations of pyrazole derivatives. Biomedicines, 10. [DOI]
- 15 Vishwakarma, 2022, Advances in tetrazole synthesis–an overview [DOI]
- 16 Trofimenko, 1972, The coordination chemistry of pyrazole-derived ligands [DOI]
- 17 Bieller, 2006, Transition metal complexes with pyrazole derivatives as ligands [DOI]
- 18 Kodadi, 2008, Synthesis of new tripodal ligand 5-(bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)amino)pentan-1-ol, catecholase activities studies of three functional tripodal pyrazolyl N-donor ligands, with different copper (II) salts [DOI]
- 19 Bouabdallah, 2007, Effect of Two Isomeric Tetrapyrazolyl Ligands on the Catalytic Oxidation of 3,5-ditert-Butylcatechol [DOI]
- 20 Yan, 2021, Highly Efficient Heteroleptic Cerium (III) Complexes with a Substituted Pyrazole Ancillary Ligand and Their Application in Blue Organic Light-Emitting Diodes [DOI]
- 21 Harit, 2017, New polymeric membrane incorporating a tetrapyrazolic macrocycle for the selective transport of cesium cation [DOI]
- 22 Harit, 2016, Synthesis and characterization of two new tetrapyrazolic macrocycles for the selective extraction of cesium cation [DOI]
- 23 Harit, 2018, Synthesis and characterization of new fluorinated copolymers based on azole groups for fuel cell membranes [DOI]
- 24 Harit, 2016, Fluorinated polymers based on pyrazole groups for fuel cell membranes [DOI]
- 25 Kumar, 2013, Pyrazole containing natural products: Synthetic preview and biological significance [DOI]
- 26 Elguero, 2000, Prototropic tautomerism of heterocycles: Heteroaromatic tautomerism-General overview and methodology [DOI]
- 27 Li, 2022, Pyrazole-containing pharmaceuticals: Target, pharmacological activity, and their SAR studies [DOI]
- 28 Katritzky, 2001, Quantitative Measures of Aromaticity for Mono-, Bi-, and Tricyclic Penta- and Hexaatomic Heteroaromatic Ring Systems and Their Interrelationships [DOI]
- 29 Dhiman, N., Kaur, K., and Jaitak, V. (2020). Tetrazoles as anticancer agents: A review on synthetic strategies, mechanism of action and SAR studies. Bioorg Med. Chem., 28. [DOI]
- 30 Pandey, 2013, Synthesis and bioevaluation of novel 4-aminoquinoline-tetrazole derivatives as potent antimalarial agents [DOI]
- 31 Gao, 2019, Recent advances of tetrazole derivatives as potential anti-tubercular and anti-malarial agents [DOI]
- 32 Wang, 2019, Tetrazole hybrids and their antifungal activities [DOI]
- 33 He, 2011, Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors [DOI]
- 34 Gao, 2019, Current scenario of tetrazole hybrids for antibacterial activity [DOI]
- 35 Kang, 2020, Cluster/cage-based coordination polymers with tetrazole derivatives [DOI]
- 36 Li, Y.T., Yao, W.Q., Zhou, S., Xu, J.X., Lu, H., Lin, J., Hu, X.Y., and Zhang, S.K. (2021). Synthesis, fungicidal activity, and 3D-QSAR of tetrazole derivatives containing phenyloxadiazole moieties. Bioorg Med. Chem. Lett., 34. [DOI]
- 37 Soylak, 2015, Enrichment-separation and determinations of cadmium(II) and lead(II)-1-phenyl-1H-tetrazole-5-thiol chelates on Diaion SP-207 by solid phase extraction-flame atomic absorption spectrometry [DOI]
- 38 Wang, 2020, A Mn(II)-MOF with inherent missing metal-ion defects based on an imidazole-tetrazole tripodal ligand and its application in supercapacitors [DOI]
- 39 Nasrollahzadeh, 2021, Use of tetrazoles in catalysis and energetic applications: Recent developments [DOI]
- 40 Krishnan, 2020, Polybenzimidazole / tetrazole-modified poly(arylene ether) blend membranes for high temperature proton exchange membrane fuel cells [DOI]
- 41 Ostrovskii, V.A., Koldobskii, G., and Trifonov, R.E. (2008). Tetrazoles. Comprehensive Heterocyclic Chemistry III, Elsevier Science. [DOI]
- 42 Trifonov, 2006, Protolytic equilibria in tetrazoles [DOI]
- 43 Yi, 1995, Synthesis of 5-aryl and vinyl tetrazoles by the palladium-catalyzed cross-coupling reaction [DOI]
- 44 Koldobskii, 2003, 2-Substituted and 2,5-Disubstituted Tetrazoles [DOI]
- 45 Faria, 2013, Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp [DOI]
- 46 Faioes, 2014, Effectiveness of novel 5-(5-amino-1-aryl-1H-pyrazol-4-yl)-1H-tetrazole derivatives against promastigotes and amastigotes of Leishmania amazonensis [DOI]
- 47 Mairink, 2013, Chemoselective and Regiospecific Formylation of 1-Phenyl-1H-pyrazoles Through the Duff Reaction [DOI]
- 48 Martins, 2013, Synthesis, docking studies, pharmacological activity and toxicity of a novel Pyrazole derivative (LQFM 021)—Possible effects on phosphodiesterase [DOI]
- 49 Florentino, 2017, New pyrazole derivative 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole: Synthesis and assessment of some biological activities [DOI]
- 50 Florentino, 2015, Involvement of the NO/cGMP/KATP pathway in the antinociceptive effect of the new pyrazole 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-021) [DOI]
- 51 Ravula, 2016, Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents
- 52 Mason, D.T., and Foerster, J.M. (1981). Side Effects and Intoxication of Cardiac Glycosides: Manifestations and Treatment. Cardiac Glycosides Handbook of Experimental Pharmacology, Springer. [DOI]
- 53 Hauptman, 1999, Digitalis [DOI]
- 54 Duan, 2015, Design and discovery of 2-(4-(1H-tetrazol-5-yl)-1H-pyrazol-1-yl)-4-(4-phenyl)thiazole derivatives as cardiotonic agents via inhibition of PDE3 [DOI]
- 55 Kaushik, 2016, Synthesis, Antioxidant and Antidiabetic Activity of 1-[(5-Substituted phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-5-phenyl-1H-tetrazole [DOI]
- 56 Mao, 2016, Design and Development of Novel 4-(4-(1H-Tetrazol-5-yl)-1H-pyrazol-1-yl)-6-morpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine as Cardiotonic Agent via Inhibition of PDE3 [DOI]
- 57 Kumbar, 2018, Synthesis, Photophysical and Computational Study of Novel Coumarin-based Organic Dyes [DOI]
- 58 Kattimani, 2019, Novel 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles as glycogen phosphorylase inhibitors: An in vivo antihyperglycemic activity study [DOI]
- 59 Kushwaha, 2019, Synthesis, biological evaluation and molecular dynamic simulations of novel Benzofuran-tetrazole derivatives as potential agents against Alzheimer’s disease [DOI]
- 60 Kumbar, 2018, 5-(1-Aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles: Synthesis, structural characterization, Hirshfeld analysis, anti-inflammatory and anti-bacterial studies [DOI]
- 61 Lempert, 2018, Energetic abilities of nitro derivatives of isomeric (pyrazol-3-yl)tetrazoles as components of solid composite propellants [DOI]
- 62 Dhevaraj, 2019, Synthesis, characterization, molecular docking, ADME and biological evaluation of 3-(4-(tetrazol-1-yl)phenyl)-5-phenyl-1H-pyrazoles [DOI]
- 63 Ashok, 2019, Microwave Assisted Synthesis of 5-[4-(3-Phenyl-4,5-dihydro-1H-pyrazol-5-yl)phenyl]-1H-tetrazole Derivatives and Their Antimicrobial Activity [DOI]
- 64 Dofe, 2018, Ultrasound-assisted synthesis and antimicrobial activity of tetrazole-based pyrazole and pyrimidine derivatives [DOI]
- 65 Elmonaem, 2018, Synthesis, In Vitro Antiproliferative Evaluation and Molecular Docking of New tetrazole-chalcone and tetrazole-pyrazoline Hybrids
- 66 Nesterova, 2017, Synthesis and structure of N-(4,6-dimethylpyrimidin-2-yl)-2-(5-phenyl-2H-tetrazol-2-yl)acetohydrazide and 1-(4,6-dimethylpyrimidin-2-yl)-3-[(5-phenyl-2H-tetrazol-2-yl)methyl]-1H-pyrazol-5-ol [DOI]
- 67 Vatsadze, 2015, Synthesis of 1-(N-nitropyrazolyl)-1H-tetrazoles—A new type of heteronuclear N-nitropyrazole derivatives [DOI]
- 68 Kumar, 2017, N-Acetonitrile Functionalized Nitropyrazoles: Precursors to Insensitive Asymmetric N-Methylene-C Linked Azoles [DOI]
- 69 Kumar, 2016, Connecting energetic nitropyrazole and aminotetrazole moieties with N,N′-ethylene bridges: A promising approach for fine tuning energetic properties [DOI]
- 70 Kumar, 2016, Asymmetric N,N′-ethylene-bridged azole-based compounds: Two way control of the energetic properties of compounds [DOI]
- 71 Kumar, 2017, Resolving synthetic challenges faced in the syntheses of asymmetric N,N′-ethylene-bridged energetic compounds [DOI]
- 72 Kazakov, 2018, Pyrazolyltetrazoles—A High-Enthalpy Backbone for Designing High-Energy Compounds: An Experimental Study of the Enthalpy of Formation [DOI]
- 73 Zheng, 2020, Synthesis of 5-(1H-pyrazol-1-yl)-2H-tetrazole-derived energetic salts with high thermal stability and low sensitivity [DOI]
- 74 Cherfi, 2021, Synthesis and characterization of new pyrazole-tetrazole derivatives as new vasorelaxant agents [DOI]
- 75 Harit, 2022, Hybrid Pyrazole-Tetrazole Derivatives with High α-Amylase Inhibition Activity: Synthesis, Biological Evaluation and Docking Study [DOI]
- 76 Oulous, 2022, New pyrazole-tetrazole hybrid compounds as potent alpha-amylase and non-enzymatic glycation inhibitors [DOI]
- 77 Cherfi, 2023, Pyrazole-tetrazole hybrid compounds: Synthesis, characterization and their biological activities [DOI]
- 78 Yin, 2014, Energetic N,N′-ethylene-bridged bis(nitropyrazoles): Diversified functionalities and properties [DOI]
- 79 Joo, 2009, Energetic mono-, di-, and trisubstituted nitroiminotetrazoles [DOI]
- 80 Sproll, 2009, Alkyl-Bridged Bis-5-azidotetrazoles: A Safe Way of Preparation [DOI]
Cited by 30
Ahmad Sajjadi, Vicky Jain, Suhas Ballal · RSC Advances · 2025
Showing 11 of 30 known citations — external sources report more than can currently be individually listed.
Related research
- A Novel Catalytic Synthesis of Flavones under Autoclave Conditions and Comparative Study of Anti-cancer Activity — shares topic coverage
- Thermostability and in-vitro Antibacterial Activity of Aqueous Extracts of Tetrapleura tetraptera Pods on Multidrug Resistant Clinical Isolates — shares topic coverage
- Acute Toxicity, Phytochemistry and Anti-diarrheal Effects of Celtis integrifolia Lam. Aqueous Leaf Extract in Wistar Albino Rats — shares topic coverage
- Understanding the Reactivity of Trimethylsilyldiazoalkanes Participating in [3+2] Cycloaddition Reactions towards Diethylfumarate with a Molecular Electron Density Theory Perspective — shares topic coverage
- Understanding the Origin of the Regioselectivity in Non-Polar [3+2] Cycloaddition Reactions through the Molecular Electron Density Theory — shares topic coverage
Article metrics
Real usage data collected on this platform.
0
Page views
0
PDF downloads
0
Outbound clicks
30
Citations
Views by country
Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".
No views recorded yet.
Traffic sources
Referring site, by host.
No traffic recorded yet.
Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.