Skip to main content

Pyrazoles, Indazoles and Pyrazolines: Recent Developments and Their Properties

  • Chapter
  • First Online:
N-Heterocycles

Abstract

Heterocyclic compounds with nitrogen atom in the ring are very important scaffold in the synthesis of many medicinal compounds and agricultural compounds and played a crucial role in drug design. Pyrazole, indazole and pyrazolines showed many pharmacological properties which are anticonvulsant, antioxidant, antibacterial, fungicides, antiviral, anti-inflammatory, antidepressant, anti-inflammatory, anti-tubercular, anticancer, and antipyretic. Recently, these have gained attention due to their photo-physical properties in the form of OLED devices. That is why their synthesis gained attention nowadays.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Ahmet MT, Douglas KT, Silver J et al (1986) Iron and haem complexation studies of 2, 3-dihydro-1H-imidazo (1,2-b) pyrazole (IMPY, NSC 51143), a tumour cell ribonucleotide reductase inhibitor. Anti-Cancer Drug Des 1:189–195

    CAS  Google Scholar 

  • Amnerkar ND, Bhusari KP (2010) Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. Eur J Med Chem 45:149–159

    Article  CAS  PubMed  Google Scholar 

  • Abdel-Wahab BF, Abdel-Aziz HA, Ahmed EM (2009) Synthesis and antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles. Eur J Med Chem 44:2632–2635

    Article  CAS  PubMed  Google Scholar 

  • Asad M, Khan SA, Arshad MN et al (2021) Design and synthesis of novel pyrazoline derivatives for their spectroscopic, single crystal X-ray and biological studies. J Mol Struct 1234:130131

    Google Scholar 

  • Annes SB, Vairaprakash P, Ramesh S (2018) TfOH mediated intermolecular electrocyclization for the synthesis of pyrazolines and its application in alkaloid synthesis. RSC Adv 8:30071–30075

    Article  CAS  Google Scholar 

  • Akhtar W, Khan MF, Verma G et al (2017) Coumarin-pyrazoline derivatives: their one-pot microwave assisted synthesis and antimalarial activity. J Pharm Med Chem 3:5–9

    Google Scholar 

  • Budakoti A, Bhat AR, Azam A (2009) Synthesis of new 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1, 3-thiazolino [5,4-b] quinoxaline derivatives and evaluation of their antiamoebic activity. Eur J Med Chem 44:1317–1325

    Article  CAS  PubMed  Google Scholar 

  • Bardalai DB (2012) Pyrazole and 2-Pyrazoline derivatives: potential anti-inflammatory and analgesic agents. Int J Appl Pharm Sci Res 2:1–8

    CAS  Google Scholar 

  • Beyzaei H, Motraghi Z, Aryan R et al (2017) Green one-pot synthesis of novel polysubstituted pyrazole derivatives as potential antimicrobial agents. Acta Chim Slov 64:911–918

    Article  CAS  PubMed  Google Scholar 

  • Bhat P, Shridhar G, Ladage S et al (2017) An eco-friendly synthesis of 2-pyrazoline derivatives catalysed by CeCl3·7H2O. J Chem Sci 129:1441–1448

    Article  CAS  Google Scholar 

  • Clapham KM, Batsanov AS, Bryce MR et al (2009) Trifluoromethyl-substituted pyridyl-and pyrazolylboronic acids and esters: synthesis and Suzuki-Miyaura cross-coupling reactions. Org Biomol Chem 7:2155–2161

    Article  CAS  PubMed  Google Scholar 

  • Damljanović I, Vukićević M, Radulović N et al (2009) Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit. Bioorganic Med Chem Lett 19:1093–1096

    Article  CAS  Google Scholar 

  • Desai NC, Rajpara KM, Joshi VV (2013) Synthesis of pyrazole encompassing 2-pyridone derivatives as antibacterial agents. Bioorganic Med Chem Lett 23:2714–2717

    Article  CAS  Google Scholar 

  • Eicher T, Hauptmann S, Speicher A (2013) The chemistry of heterocycles: structures, reactions, synthesis, and applications. John Wiley & Sons

    Google Scholar 

  • Elguero J, Goya P, Jagerovic N et al (2002) Targets Heterocycl. Syst. 6:52

    CAS  Google Scholar 

  • Ebrahimzadeh MA, Pourmorad F (2016) Synthesis and antimicrobial activity of some 3-aryl-5-imidazolyl-2-pyrazolines. Int J Life Sci Pharmaceu Res 6:L-38-L43

    Google Scholar 

  • Ebrahimzadeh MA, Pourmorad F, Mahmoudi M, Haghighi S, Nourbakhsh Z and Javanmardi A (2004) Preparation of some analgesic dihydropyridine derivatives. Chem An Indian J 1:338–343

    Google Scholar 

  • Farmani HR, Mosslemin MH, Sadeghi B (2018) Microwave-assisted green synthesis of 4, 5-dihydro-1H-pyrazole-1-carbothioamides in water. Mol Divers 22:743–749

    Article  CAS  PubMed  Google Scholar 

  • Fatima F, Bhat SH, Ullah MF et al. (2018) Abu-Duhier, F.; Husain, E. In-Vitro antimicrobial activity of herbal extracts from Tabuk Region (Kingdom of Saudi Arabia) against nosocomial pathogens: a preliminary study. Glob J Health Sci 10:1–83

    Google Scholar 

  • Goddard AJ, Orr RM, Stock JA et al (1987) Synthesis and ribonucleotide reductase inhibitory activity of analogues of 2,3-dihydro-1H-imidazo [1,2-b] pyrazole (IMPY). Anti-Cancer Drug Des 2:235–245

    CAS  Google Scholar 

  • Gopalakrishnan M, Thanusu J, Kanagarajan V (2009) A new series of fused indazole derivatives: solid state synthesis; antibacterial and antifungal activities. Pharmaceut Chem J 43:30–35

    Article  CAS  Google Scholar 

  • Ghosh S, Samanta S, Ghosh AK et al (2020) Advances in oxosulfonylation reaction. Adv Synth Catal 362:4552–4578

    Article  CAS  Google Scholar 

  • Ghosh S, Mondal S, Hajra A (2020) Direct catalytic functionalization of indazole derivatives. Adv Synth Catal 362:3768–3794

    Article  CAS  Google Scholar 

  • Hegde H, Ahn C, Gaonkar SL et al (2017) Synthesis of new pyrazoline derivatives and its antimicrobial and antioxidant activities. J Korean Chem Soc 61:291–295

    CAS  Google Scholar 

  • Jasril J, Teruna HY, Aisyah A et al (2019) Microwave assisted synthesis and evaluation of toxicity and antioxidant activity of pyrazoline derivatives. Indones J Chem 19:583–591

    Article  CAS  Google Scholar 

  • Kumar V, Kaur K, Gupta GK et al (2013) Pyrazole containing natural products: synthetic preview and biological significance. Eur J Med Chem 69:735–753

    Article  CAS  PubMed  Google Scholar 

  • Keter FK, Darkwa J (2012) Perspective: the potential of pyrazole-based compounds in medicine. Biometals 25:9–21

    Article  CAS  PubMed  Google Scholar 

  • Kaur R, Ambwani S, Singh S (2016) Endocannabinoid system: a multi-facet therapeutic target. Curr Clin Pharmacol 11:110–117

    Article  CAS  PubMed  Google Scholar 

  • KasımoÄŸulları R, Bülbül M, Arslan BS et al (2010) Synthesis, characterization and antiglaucoma activity of some novel pyrazole derivatives of 5-amino-1, 3, 4-thiadiazole-2-sulfonamide. Eur J Med Chem 45:4769–4773

    Article  PubMed  CAS  Google Scholar 

  • Kalyani D, Sagar D, Dhanashree G (2020) Review on synthesis of pyrazoline derivatives and its biological activities. Int J Creative Res Thoughts 8:1758–1782

    Google Scholar 

  • Komendantova AS, Lyssenko KA, Zavarzin IV et al (2020) Iodine-promoted synthesis of pyrazoles from 1, 3-dicarbonyl compounds and oxamic acid thiohydrazides. Org Chem Front 7:1640–1646

    Article  CAS  Google Scholar 

  • Kumar M, Sharma S, Tuli HS et al (2019) Ferrocenyl substituted pyrazoles, synthesis via novel route, spectral investigations and their biological studies. Orient J Chem 35:863

    Article  CAS  Google Scholar 

  • Konwar M, Elnagdy HM, Gehlot PS et al (2019) Transition metal containing ionic liquid-assisted one-pot synthesis of pyrazoles at room temperature. J Chem Sci 131:1–9

    Article  CAS  Google Scholar 

  • Kaldhi D, Gujjarappa R, Vodnala N et al (2019) Mo (VI)-catalyzed Synthesis of 2-Aryl-2 H-indazoles using pinacol mediated deoxygenation of nitroaromatics. Chem Lett 48:1258–1261

    Article  CAS  Google Scholar 

  • Kaka KN, Taher SG, Hamad WM et al (2019) Synthesis of new series of pyrazoline, and study their kinetics and reaction mechanism. ARO-the Scient J Koya Univer 7:5–13

    Article  Google Scholar 

  • Kedjadja A, Bouraiou A, Merdes R (2018) Synthesis and spectral characterization of novel 2-pyrazoline and bis-2-pyrazoline containing quinoline moiety. Int J Org Chem 8:105–114

    Article  CAS  Google Scholar 

  • Kotra V, Ganapaty S, Adapa SR (2010) Synthesis of a new series of quinolinyl chalcones as anticancer and anti-inflammatory agents. Ind J Chem (sec b) 49:1109–1116

    Google Scholar 

  • Karangiya K, Upadhyay J (2016) Synthesis and antimicrobial screening of new pyrazolines derived from chalcones of vanillin Analog. Int J Pharmaceut Sci Drug Res 8:98–102

    CAS  Google Scholar 

  • Lv PC, Li HQ, Sun J et al (2010) Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg Med Chem 18:4606–4614

    Article  CAS  PubMed  Google Scholar 

  • Lo HY, Man CC, Fleck RW et al (2010) Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain. Bioorganic Med Chem Lett 20:6379–6383

    Article  CAS  Google Scholar 

  • Liu M, Zhang J (2016) Synthesis and fluorescence of pyrazolines substituted with pyrimidine and ferrocene subunits. Heterocycl Commun 22:31–35

    Article  CAS  Google Scholar 

  • Lu Z, Jiang Q, Zhu W et al (2000) Efficient blue emission from pyrazoline organic light emitting diodes. Synth Met 111:425–427

    Article  Google Scholar 

  • Mane A, Salokhe P, More P et al (2015) An efficient practical chemo-enzymatic protocol for the synthesis of pyrazoles in aqueous medium at ambient temperature. J Mol Catal B Enzym 121:75–81

    Article  CAS  Google Scholar 

  • Malapati P, Krishna VS, Dharmarajan S (2018) Identification and development of novel indazole derivatives as potent bacterial peptidoglycan synthesis inhibitors. Int J Mycobacteriol 7:76

    Article  CAS  PubMed  Google Scholar 

  • Mantzanidou M, Pontiki E, Hadjipavlou-Litina D (2021) Pyrazoles and pyrazolines as anti-inflammatory agents. Molecules 26:3439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosti L, Menozzi G, Fossa P et al (1992) 4-substituted 1-methyl-1H-indazoles with analgesic, antiinflammatory and antipyretic activities. Farmaco 47:567–584

    CAS  PubMed  Google Scholar 

  • Noe FF, Fowden L (1959) Α-amino-β-(pyrazolyl-N) propionic acid: a new amino-acid from Citrullus vulgaris (water melon). Nature 184:BA69–BA70

    Google Scholar 

  • Özdemir Z, Kandilci HB, Gümüşel B et al (2007) Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 42:373–379

    Article  PubMed  CAS  Google Scholar 

  • Persson T, Nielsen J (2006) Synthesis of N-methoxy-N-methyl-β-enaminoketoesters: new synthetic precursors for the regioselective synthesis of heterocyclic compounds. Org Lett 8:3219–3222

    Article  CAS  PubMed  Google Scholar 

  • Park HJ, Lee K, Park SJ et al (2005) Identification of antitumor activity of pyrazole oxime ethers. Bioorganic Med Chem Lett 15:3307–3312

    Article  CAS  Google Scholar 

  • Pathak RB, Chovatia PT, Parekh HH (2012) Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Bioorganic Med Chem Lett 22:5129–5133

    Article  CAS  Google Scholar 

  • Philipp Stoessel HH, Jooseten D, Pflumm C et al (2010) WO2010086089 A1

    Google Scholar 

  • Padmaja A, Rajasekhar C, Muralikrishna A et al (2011) Synthesis and antioxidant activity of oxazolyl/thiazolylsulfonylmethyl pyrazoles and isoxazoles. Eur J Med Chem 46:5034–5038

    Article  CAS  PubMed  Google Scholar 

  • Pavia DL (2009) Introduction to spectroscopy. Brooks & Cole: New York

    Google Scholar 

  • Punyapreddiwar ND, Wankhade AV, Zodape SP et al (2016) Saccharomyces cerevisiae catalyzed cyclocondensation reaction: synthesis of pyrazoline. J Appl Chem 2016:4

    Google Scholar 

  • Rangaswamy J, Kumar HV, Harini ST et al (2012) Synthesis of benzofuran based 1, 3, 5-substituted pyrazole derivatives: as a new class of potent antioxidants and antimicrobials-A novel accost to amend biocompatibility. Bioorganic Med Chem Lett 22:4773–4777

    Article  CAS  Google Scholar 

  • Ragab FA, Gawad NMA, Georgey HH et al (2013) Synthesis of novel 1, 3, 4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents. Eur J Med Chem 63:645–654

    Article  CAS  PubMed  Google Scholar 

  • Rey M, Beaumont S (2019) Molybdenum-mediated one-pot synthesis of pyrazoles from isoxazoles. Synthesis 51:3796–3804

    Article  CAS  Google Scholar 

  • Rakhtshah J, Salehzadeh S, Gowdini E et al (2016) Synthesis of pyrazole derivatives in the presence of a dioxomolybdenum complex supported on silica-coated magnetite nanoparticles as an efficient and easily recyclable catalyst. RSC Adv 6:104875–104885

    Article  CAS  Google Scholar 

  • Rüchardt C, Hassmann V (1972) Simplification of the Jacobson indazole-synthesis. Synthesis 375

    Google Scholar 

  • Ruechardt C, Sauer J, Sustmann R (2005) Rolf huisgen: some highlights of his contributions to organic chemistry. Helv Chim Acta 88:1154–1184

    Article  CAS  Google Scholar 

  • Revanasiddappa BC, Kumar MV, Kumar H (2020) Synthesis and antidepressant activity of pyrazoline derivatives. Dhaka Univ. J. Pharm. Sci. 19:179–184

    Article  CAS  Google Scholar 

  • Åžener A, Kasim Åžener M, Bildmci I et al (2002) Studies on the reactions of cyclic oxalyl compounds with hydrazines or hydrazones: Synthesis and reactions of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid. J Heterocycl Chem 39:869–875

    Article  Google Scholar 

  • Se-Ho K, Benjamin M, Richard T et al (2013) Discovery of a new HIV-1 inhibitor scaffold and synthesis of potential prodrugs of indazoles. Bioorg Med Chem Lett 23:2888–2892

    Article  CAS  Google Scholar 

  • Swathi V, Shine S, Dhanya K et al (2019) A review on the CNS activity of pyrazolines. J Med Sci Clin Res 7:612–618

    Google Scholar 

  • Sauzem PD, Sant’Anna GDS, Machado P et al (2009) Effect of 5-trifluoromethyl-4, 5-dihydro-1H-pyrazoles on chronic inflammatory pain model in rats. Eur J Pharmacol 616:91–100

    Article  CAS  PubMed  Google Scholar 

  • Shaharyar M, Abdullah MM, Bakht MA et al (2010) Pyrazoline bearing benzimidazoles: search for anticancer agent. Eur J Med Chem 45:114–119

    Article  CAS  PubMed  Google Scholar 

  • Sano T, Fujii T, Nishio Y et al (1995) Pyrazoline dimers for hole transport materials in organic electroluminescent devices. Jpn J Appl Phys 34:3124

    Article  CAS  Google Scholar 

  • Soltanzadeh Z, Imanzadeh G, Noroozi-Pesyan N et al (2017) Green synthesis of pyrazole systems under solvent-free conditions. Green Chem Lett Rev 10:148–153

    Article  CAS  Google Scholar 

  • Solomin VV, Seins A, Jirgensons A (2021) Synthesis of indazoles from 2-formylphenylboronic acids. RSC Adv 11:22710–22714

    Article  CAS  Google Scholar 

  • Shamsabadi A, Chudasama V (2018) A facile route to 1 H-and 2 H-indazoles from readily accessible acyl hydrazides by exploiting a novel aryne-based molecular rearrangement. Chem Commun 54:11180–11183

    Article  CAS  Google Scholar 

  • Sirven AM, Stefak R, Rapenne G (2015) Improved synthesis of 6-[(ethylthio) methyl]-1H-indazole. Heterocycl Commun 21:5–8

    Article  CAS  Google Scholar 

  • Spackman MA, Jayatilaka D (2009) Hirshfeld surface analysis. Cryst Eng Comm 11:19–32

    Google Scholar 

  • Sultan MI, Abdula AM, Faeq RI et al (2021) Synthesis, characterization, and antimicrobial evaluation of new pyrazolines incorporating imine moiety. In J Phy Conf Ser 1853:012043

    Google Scholar 

  • Sethiya JP, Bhavsar SP, Shahare HV (2019) Synthesis of potential anti-inflammatory pyrazoline derivatives under ultrasonic irradiation. Int J Pharmaceu Sci Res 10:3290–3294

    CAS  Google Scholar 

  • Salim AS, Girgis AS, Basta AH et al (2018) Comparative DFT computational studies with experimental investigations for novel synthesized fluorescent pyrazoline derivatives. J Fluoresc 28:913–931

    Article  CAS  PubMed  Google Scholar 

  • Tafti AD, Mirjalili BBF, Bamoniri A et al (2021) Rapid four component synthesis of dihydropyrano [2, 3-c] pyrazoles using nano-eggshell/Ti (IV) as a highly compatible natural based catalyst. BMC Chem 15:1–8

    CAS  Google Scholar 

  • Tanwar N, Rana D, Kaur R et al (2015) Synthesis and characterization of Pyrazoline derivatives. J Integr Sci Technol 3:39–41

    Google Scholar 

  • Vicentini CB, Romagnoli C, Andreotti E et al (2007) Synthetic pyrazole derivatives as growth inhibitors of some phytopathogenic fungi. J Agric Food Chem 55:10331–10338

    Article  CAS  PubMed  Google Scholar 

  • Wrzeciono U, Linkowska E, Majewska K et al (1993) Synthesis and anti-inflammatory activity of some indazole derivatives. 36. Azoles Pharmazie 48:582–584

    CAS  PubMed  Google Scholar 

  • Westermeyer A, Llopis Q, Guillamot G et al (2020) Highly regioselective synthesis of 3, 5-substituted pyrazoles from bromovinyl acetals and N-tosylhydrazones. Synlett 31:1172–1176

    Article  CAS  Google Scholar 

  • Wahyuningsih TD, Suma AAT, Astuti E (2019) Synthesis, anticancer activity, and docking study of N-acetyl pyrazolines from veratraldehyde. J Appl Pharm Sci 9:14–20

    Article  CAS  Google Scholar 

  • Wan Y, He S, Li W et al (2018) Indazole derivatives: promising anti-tumor agents. Anticancer Agents Med Chem 18:1228–1234

    Article  CAS  PubMed  Google Scholar 

  • Yang B, Li Y, Xu CX (2003) The progress of organic flurescent materials. Chem Res Appl 15:11–16

    Google Scholar 

  • Young RH, Fitzgerald JJ (1995) Dipole moments of hole-transporting materials and their influence on hole mobility in molecularly doped polymers. J Phys Chem 99:4230–4240

    Article  CAS  Google Scholar 

  • Zhang T, Dong M, Zhao J et al (2019) Synthesis and antifungal activity of novel pyrazolines and isoxazolines derived from cuminaldehyde. J Pestici Sci 44:181–185

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gupta, S.L., Saini, S., Saini, P., Dandia, A., Ameta, K.L., Parewa, V. (2022). Pyrazoles, Indazoles and Pyrazolines: Recent Developments and Their Properties. In: Ameta, K.L., Kant, R., Penoni, A., Maspero, A., Scapinello, L. (eds) N-Heterocycles. Springer, Singapore. https://doi.org/10.1007/978-981-19-0832-3_12

Download citation

Publish with us

Policies and ethics