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image of Pyridazinone: Current Progress in Synthesis of its Derivatives and Biological Activity

Abstract

Pyridazinone, a six-membered heterocyclic molecule, has emerged as an important pharmacophore in drug discovery due to its diverse range of biological actions. This adaptable scaffold has shown tremendous promise in the development of therapeutic medicines for a variety of pharmacological conditions, including anti-inflammatory, anti-cancer, anti-microbial, cardiovascular, and central nervous system illnesses. Pyridazinone derivatives are useful in medicinal chemistry due to their propensity to interact with a wide range of biological targets. This review offers a comprehensive overview of Pyridazinone-based compounds, focusing on their chemical structure, mechanism of action, structure-activity relationship (SAR), and therapeutic uses. Current trends in Pyridazinone research and its potential as a lead chemical for new medication development are also reviewed. Pyridazinone broad range of activity and adaptability highlight its importance in developing pharmacotherapy.

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2024-12-24
2025-01-24
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References

  1. Dubey S. Bhosle P.A. Pyridazinone: An important element of pharmacophore possessing broad spectrum of activity. Med. Chem. Res. 2015 24 10 3579 3598 10.1007/s00044‑015‑1398‑5
    [Google Scholar]
  2. Gates C.A. Backos D.S. Reigan P. Natale N.R. The lateral metalation of isoxazolo[3,4-d]pyridazinones towards hit-to-lead development of selective positive modulators of metabotropic glutamate receptors. Molecules 2023 28 19 6800 10.3390/molecules28196800 37836643
    [Google Scholar]
  3. Saini M. Mehta K.D. Das R. Saini G. Recent advances in anti-inflammatory potential of pyridazinone derivatives. Mini Rev. Med. Chem. 2016 16 12 996 1012 10.2174/1389557516666160611015815 27290912
    [Google Scholar]
  4. Tan O.U. Sari O.K. Azolo[d]pyridazinones in medicinal chemistry. Future Med. Chem. 2021 13 3 287 311 10.4155/fmc‑2020‑0234 33275029
    [Google Scholar]
  5. Singh J. Sharma D. Bansal R. Pyridazinone: An attractive lead for anti-inflammatory and analgesic drug discovery. Future Med. Chem. 2017 9 1 95 127 10.4155/fmc‑2016‑0194 27957866
    [Google Scholar]
  6. Hassan M.S.A. Ahmed E.M. Malah E.A.A. Kassab A.E. Anti‐inflammatory activity of pyridazinones: A review. Arch. Pharm. (Weinheim) 2022 355 8 2200067 10.1002/ardp.202200067 35532263
    [Google Scholar]
  7. Rosa F.A. Jacomini A.P. Vieira da Silva M.J. Pianoski K.E. Poletto J. Francisco C.B. de Souza Fernandes C. Martinelli V. Pontes R.M. Back D.F. Moura S. Basso E.A. Controlled pyrazole-hydrazone annulation: Regiodivergent synthesis of 1 H - and 2 H -Pyrazolo[3,4- d ]pyridazinones. J. Org. Chem. 2023 88 15 11140 11149 10.1021/acs.joc.3c01117 37463494
    [Google Scholar]
  8. Zhu Z. Tang J. Kyriazakos S. Knieb A. Xu Y. Zhang C. Prakash G.K.S. Mono- and difluoromethylation of 3(2 H )-Pyridazinones. Org. Lett. 2024 26 38 8106 8109 10.1021/acs.orglett.4c03002
    [Google Scholar]
  9. Asif M. A mini review on biological activities of pyridazinone derivatives as antiulcer, antisecretory, antihistamine and particularly against histamine H3R. Mini Rev. Med. Chem. 2015 14 13 1093 1103 10.2174/1389557514666141127143133 25429662
    [Google Scholar]
  10. Pathak S. Jain S. Pratap A. A review on synthesis and biological potential of dihydropyridines. Lett. Drug Des. Discov. 2024 21 1 15 33 10.2174/1570180820666230508100955
    [Google Scholar]
  11. Pathak S. Pandey R. Agrawal N. Anilinopyrimidines: A review exploring synthetic approaches and biological activity. Lett. Org. Chem. 2023 20 10 931 944 10.2174/1570178620666230525140626
    [Google Scholar]
  12. Agrawal N. Mishra R. Pathak S. Goyal A. Shah K. Hydrazides and hydrazones: Robust scaffolds in neurological and neurodegenerative disorders. Lett. Org. Chem. 2023 20 2 123 136 10.2174/1570178619666220831122614
    [Google Scholar]
  13. Pathak S. Sharma R. A comprehensive review on the benzimidazole scaffold as a potential nucleus for anticancer activity. Lett. Org. Chem. 2023 20 9 802 817 10.2174/1570178620666230330105103
    [Google Scholar]
  14. Pathak S. Agrawal N. Gaur S. A review on diverse biological activity of heterocyclic nucleus pyrazine and its derivatives: A key for the researchers. Lett. Org. Chem. 2024 21 4 351 361 10.2174/0115701786273932230927062616
    [Google Scholar]
  15. Agrawal N. Bansal D. Pathak S. Exploring the therapeutic marvels: A comprehensive review on the biological potential of quinoline-5,8-dione. Med. Chem. 2024 20 4 385 396 10.2174/0115734064287677231215070816 38173200
    [Google Scholar]
  16. Agrawal N. Goswami R. Pathak S. Synthetic methods for various chromeno-fused heterocycles and their potential as antimicrobial agents. Med. Chem. 2024 20 2 115 129 10.2174/0115734064274748231005074100 37855281
    [Google Scholar]
  17. Sabnis R.W. Novel pyridazinones as TRPC5 inhibitors for treating kidney diseases. ACS Med. Chem. Lett. 2021 12 4 526 527 10.1021/acsmedchemlett.1c00123 33859787
    [Google Scholar]
  18. Cantini N. Schepetkin I.A. Danilenko N.V. Khlebnikov A.I. Crocetti L. Giovannoni M.P. Kirpotina L.N. Quinn M.T. Pyridazinones and structurally related derivatives with anti-inflammatory activity. Molecules 2022 27 12 3749 10.3390/molecules27123749 35744876
    [Google Scholar]
  19. Akhtar W. Shaquiquzzaman M. Akhter M. Verma G. Khan M.F. Alam M.M. The therapeutic journey of pyridazinone. Eur. J. Med. Chem. 2016 123 256 281 10.1016/j.ejmech.2016.07.061 27484513
    [Google Scholar]
  20. Abouzid K. Bekhit S.A. Novel anti-inflammatory agents based on pyridazinone scaffold; design, synthesis and in vivo activity. Bioorg. Med. Chem. 2008 16 10 5547 5556 10.1016/j.bmc.2008.04.007 18430576
    [Google Scholar]
  21. Combs D.W. Rampulla M.S. Demers J.P. Falotico R. Moore J.B. Heteroatom analogs of bemoradan: Chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones. J. Med. Chem. 1992 35 1 172 176 10.1021/jm00079a023 1732525
    [Google Scholar]
  22. Robertson D.W. Leander J.D. Lawson R. Beedle E.E. Clark C.R. Potts B.D. Parli C.J. Discovery and anticonvulsant activity of the potent metabolic inhibitor 4-amino-N-(2,6-dimethylphenyl)-3,5-dimethylbenzamide. J. Med. Chem. 1987 30 10 1742 1746 10.1021/jm00393a010 3656350
    [Google Scholar]
  23. Archan S. Toller W. Levosimendan: Current status and future prospects. Curr. Opin. Anaesthesiol. 2008 21 1 78 84 10.1097/ACO.0b013e3282f357a5 18195615
    [Google Scholar]
  24. Avcı D. Bahçeli S. Tamer Ö. Atalay Y. Comparative study of DFT/B3LYP, B3PW91, and HSEH1PBE methods applied to molecular structures and spectroscopic and electronic properties of flufenpyr and amipizone. Can. J. Chem. 2015 93 10 1147 1156 10.1139/cjc‑2015‑0176
    [Google Scholar]
  25. Asif M. Overview on emorfazone and other related 3(2H) pyridazinone analogues displaying analgesic and anti- inflammatory activity mohammad. Ann. Med. Chem. Res. 2015 3 1 9
    [Google Scholar]
  26. Ukena D. Rentz K. Reiber C. Sybrecht G.W. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction. Respir. Med. 1995 89 6 441 444 10.1016/0954‑6111(95)90214‑7 7644776
    [Google Scholar]
  27. Ibrahim H.M. Behbehani H. Elnagdi M.H. Approaches towards the synthesis of a novel class of 2-amino-5-arylazonicotinate, pyridazinone and pyrido[2,3-d]pyrimidine derivatives as potent antimicrobial agents. Chem. Cent. J. 2013 7 1 123 10.1186/1752‑153X‑7‑123 23867062
    [Google Scholar]
  28. Abbas S.H. Rahma A.G.E.D.A.A. Aziz A.M. Aly O.M. Beshr E.A. Eldeen G.A.M. Synthesis, cytotoxic activity, and tubulin polymerization inhibitory activity of new pyrrol-2(3H)-ones and pyridazin-3(2H)-ones. Bioorg. Chem. 2016 66 46 62 10.1016/j.bioorg.2016.03.007 27016713
    [Google Scholar]
  29. Zhang X. Luo J. Li Q. Xin Q. Ye L. Zhu Q. Shi Z. Zhan F. Chu B. Liu Z. Jiang Y. Design, synthesis and anti-tumor evaluation of 1,2,4-triazol-3-one derivatives and pyridazinone derivatives as novel CXCR2 antagonists. Eur. J. Med. Chem. 2021 226 113812 10.1016/j.ejmech.2021.113812 34536673
    [Google Scholar]
  30. Ahmed E.M. Kassab A.E. Malah E.A.A. Hassan M.S.A. Synthesis and biological evaluation of pyridazinone derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents. Eur. J. Med. Chem. 2019 171 25 37 10.1016/j.ejmech.2019.03.036 30904755
    [Google Scholar]
  31. Barberot C. Moniot A. Simon A.I. Malleret L. Yegorova T. Cochard L.M. Bentaher A. Médebielle M. Bouillon J.P. Hénon E. Sapi J. Velard F. Gérard S. Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents. Eur. J. Med. Chem. 2018 146 139 146 10.1016/j.ejmech.2018.01.035 29407945
    [Google Scholar]
  32. Bashir R. Yaseen S. Ovais S. Ahmad S. Hamid H. Alam M.S. Samim M. Javed K. Synthesis and biological evaluation of some novel sulfamoylphenyl-pyridazinone as anti-inflammatory agents (Part-II). J. Enzyme Inhib. Med. Chem. 2012 27 1 92 96 10.3109/14756366.2011.577036 21612377
    [Google Scholar]
  33. Gökçe M. Fethi M. ¸ahin S. Küpeli E. Yes¸ilada E.Y. Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives. Arzneimittelforschung. 2004 54 7 396 401
    [Google Scholar]
  34. Husain A. Drabu S. Kumar N. Alam M.M. Ahmad A. Synthesis and biological evaluation of some new pyridazinone derivatives. J. Enzyme Inhib. Med. Chem. 2011 26 5 742 748 10.3109/14756366.2010.548810 21271866
    [Google Scholar]
  35. Loksha Y.M. Alhaseeb A.M.M. Synthesis and biological screening of some novel 6‐substituted 2‐alkylpyridazin‐3(2 H )‐ones as anti‐inflammatory and analgesic agents. Arch. Pharm. 2020 353 3 1900295 10.1002/ardp.201900295 31944384
    [Google Scholar]
  36. Kilic B. Erdogan M. Gulcan H.O. Aksakal F. Oruklu N. Bagriacik E.U. Dogruer D.S. Design, synthesis and investigation of new diphenyl substituted pyridazinone derivatives as both cholinesterase and Aβ-aggregation inhibitors. Med. Chem. 2019 15 1 59 76 10.2174/1573406414666180524073241 29792155
    [Google Scholar]
  37. Pau A. Catto M. Pinna G. Frau S. Murineddu G. Asproni B. Curzu M.M. Pisani L. Leonetti F. Loza M.I. Brea J. Pinna G.A. Carotti A. Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors. ChemMedChem 2015 10 6 1054 1070 10.1002/cmdc.201500124 25924828
    [Google Scholar]
  38. Liu Y. Jin S. Peng X. Lu D. Zeng L. Sun Y. Ai J. Geng M. Hu Y. Pyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase. Eur. J. Med. Chem. 2016 108 322 333 10.1016/j.ejmech.2015.11.042 26698536
    [Google Scholar]
  39. Çeçen M. Oh J.M. Özdemir Z. Büyüktuncel S.E. Uysal M. Abdelgawad M.A. Musa A. Gambacorta N. Nicolotti O. Mathew B. Kim H. Design, synthesis, and biological evaluation of pyridazinones containing the (2-fluorophenyl) piperazine moiety as selective mao-b inhibitors. Molecules 2020 25 22 5371 10.3390/molecules25225371 33212876
    [Google Scholar]
  40. Ovais S. Javed K. Yaseen S. Bashir R. Rathore P. Yaseen R. Hameed A.D. Samim M. Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones. Eur. J. Med. Chem. 2013 67 352 358 10.1016/j.ejmech.2013.06.050 23887055
    [Google Scholar]
  41. Abubshait S.A. An efficient synthesis and reactions of novel indolyl-pyridazinone derivatives with expected biological activity. Molecules. 2007 12 1 25 42
    [Google Scholar]
  42. Abouzid K. Hakeem A.M. Khalil O. Maklad Y. Pyridazinone derivatives: Design, synthesis, and in vitro vasorelaxant activity. Bioorg. Med. Chem. 2008 16 1 382 389 10.1016/j.bmc.2007.09.031 17905589
    [Google Scholar]
  43. Rahman A.H.M. Aziz A.M. Tinsley H.N. Gary B.D. Canzoneri J.C. Piazza G.A. Design and synthesis of substituted pyridazinone‐1‐acetylhydrazones as novel phosphodiesterase 4 inhibitors. Arch. Pharm. (Weinheim) 2016 349 2 104 111 10.1002/ardp.201500363 26686665
    [Google Scholar]
  44. Biagini P. Biancalani C. Graziano A. Cesari N. Giovannoni M.P. Cilibrizzi A. Piaz V.D. Vergelli C. Crocetti L. Delcanale M. Armani E. Rizzi A. Puccini P. Gallo P.M. Spinabelli D. Caruso P. Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity. Bioorg. Med. Chem. 2010 18 10 3506 3517 10.1016/j.bmc.2010.03.066 20413313
    [Google Scholar]
  45. Gràcia J. Buil M.A. Castro J. Eichhorn P. Ferrer M. Gavaldà A. Hernández B. Segarra V. Lehner M.D. Moreno I. Pagès L. Roberts R.S. Serrat J. Sevilla S. Taltavull J. Andrés M. Cabedo J. Vilella D. Calama E. Carcasona C. Miralpeix M. Biphenyl pyridazinone derivatives as inhaled pde4 inhibitors: Structural biology and structure–activity relationships. J. Med. Chem. 2016 59 23 10479 10497 10.1021/acs.jmedchem.6b00829 27933955
    [Google Scholar]
  46. Simon A.I. Moniot A. Bisi N. Vargas P.M. Audonnet S. Cochard L.M. Sapi J. Hénon E. Velard F. Gérard S. Pyridazinone derivatives as potential anti-inflammatory agents: Synthesis and biological evaluation as PDE4 inhibitors. RSC Med. Chem. 2021 12 4 584 592 10.1039/D0MD00423E 34046629
    [Google Scholar]
  47. Amin E.N. Alim A.A.A.M. Moty A.S.G. Shorbagi E.A.N.A. Rahman A.M.S. Synthesis of new 4,5-3(2H)pyridazinone derivatives and their cardiotonic, hypotensive, and platelet aggregation inhibition activities. Arch. Pharm. Res. 2010 33 1 25 46 10.1007/s12272‑010‑2222‑x 20191341
    [Google Scholar]
  48. Costas T. Lago C.M.C. Vila N. Besada P. Cano E. Terán C. New platelet aggregation inhibitors based on pyridazinone moiety. Eur. J. Med. Chem. 2015 94 113 122 10.1016/j.ejmech.2015.02.061 25757094
    [Google Scholar]
  49. Besada P. Viña D. Costas T. Lago C.M.C. Vila N. Terán T.I. Sturlese M. Moro S. Terán C. Pyridazinones containing dithiocarbamoyl moieties as a new class of selective MAO-B inhibitors. Bioorg. Chem. 2021 115 105203 10.1016/j.bioorg.2021.105203 34371375
    [Google Scholar]
  50. Özdemir Z. Alagöz M.A. Uslu H. Karakurt A. Erikci A. Ucar G. Uysal M. Synthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitors. Pharmacol. Rep. 2020 72 3 692 704 10.1007/s43440‑020‑00070‑w 32144745
    [Google Scholar]
  51. Sukuroglu M. Onkol T. Onurdağ F.K. Akalın G. Şahin M.F. Synthesis and in vitro biological activity of new 4,6-disubstituted 3(2H)-pyridazinone-acetohydrazide derivatives. Z. Naturforsch. C J. Biosci. 2012 67 5-6 257 265 10.1515/znc‑2012‑5‑604 22888530
    [Google Scholar]
  52. Abdelbaset M.S. Rahma A.G.E.D.A. Abdelrahman M.H. Ramadan M. Youssif B.G.M. Bukhari S.N.A. Mohamed M.F.A. Aziz A.M. Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors. Bioorg. Chem. 2018 80 151 163 10.1016/j.bioorg.2018.06.003 29920422
    [Google Scholar]
  53. Wu X. Dai M. Cui R. Wang Y. Li C. Peng X. Zhao J. Wang B. Dai Y. Feng D. Yang T. Jiang H. Geng M. Ai J. Zheng M. Liu H. Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyridazinone derivatives as covalent FGFR inhibitors. Acta Pharm. Sin. B 2021 11 3 781 794 10.1016/j.apsb.2020.09.002 33777682
    [Google Scholar]
  54. Murineddu G. Cignarella G. Chelucci G. Loriga G. Pinna G.A. Synthesis and cytotoxic activities of pyrrole [2, 3-d] pyridazin-4-one derivatives. Chem. pharm. bul. 2002 50 6 754 759
    [Google Scholar]
  55. Gutierrez D.A. DeJesus R.E. Contreras L. Palomares R.I.A. Villanueva P.J. Balderrama K.S. Monterroza L. Larragoity M. Ramirez V.A. Aguilera R.J. A new pyridazinone exhibits potent cytotoxicity on human cancer cells via apoptosis and poly-ubiquitinated protein accumulation. Cell Biol. Toxicol. 2019 35 6 503 519 10.1007/s10565‑019‑09466‑8 30825052
    [Google Scholar]
  56. Krasavin M. Shetnev A. Baykov S. Kalinin S. Nocentini A. Sharoyko V. Poli G. Tuccinardi T. Korsakov M. Tennikova T.B. Supuran C.T. Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines. Eur. J. Med. Chem. 2019 168 301 314 10.1016/j.ejmech.2019.02.044 30826507
    [Google Scholar]
  57. Alagöz M.A. Özdemir Z. Uysal M. Carradori S. Gallorini M. Ricci A. Zara S. Mathew B. Synthesis, cytotoxicity and anti-proliferative activity against ags cells of new 3(2H)-pyridazinone derivatives endowed with a piperazinyl linker. Pharmaceuticals 2021 14 3 183 10.3390/ph14030183 33668893
    [Google Scholar]
  58. Bender S.M. Wiatrak B. Dzimira S. Merwid-Ląd A. Szczukowski Ł. Świątek P. Szeląg A. Targeting lineage-specific transcription factors and cytokines of the th17/treg axis by novel 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone attenuates TNBS-induced experimental colitis. Int. J. Mol. Sci. 2022 23 17 9897 10.3390/ijms23179897 36077306
    [Google Scholar]
  59. Singh J. Saini V. Kumar A. Bansal R. Synthesis, molecular docking and biological evaluation of some newer 2-substituted-4-(benzo[ d ][1,3]dioxol-5-yl)-6-phenylpyridazin-3(2 H )-ones as potential anti-inflammatory and analgesic agents. Bioorg. Chem. 2017 71 201 210 10.1016/j.bioorg.2017.02.006 28236449
    [Google Scholar]
  60. Kim E.Y. Kang S.T. Jung H. Park C.H. Yun C.S. Hwang J.Y. Byun B.J. Lee C.O. Kim H.R. Ha J.D. Ryu D.H. Cho S.Y. Discovery of substituted pyrazol-4-yl pyridazinone derivatives as novel c-Met kinase inhibitors. Arch. Pharm. Res. 2016 39 4 453 464 10.1007/s12272‑015‑0703‑7 26753914
    [Google Scholar]
  61. Lu D. Yan J. Wang L. Liu H. Zeng L. Zhang M. Duan W. Ji Y. Cao J. Geng M. Shen A. Hu Y. Design, synthesis, and biological evaluation of the first c-met/hdac inhibitors based on pyridazinone derivatives. ACS Med. Chem. Lett. 2017 8 8 830 834 10.1021/acsmedchemlett.7b00172 28835797
    [Google Scholar]
  62. Liu X. Kou J. Xiao Z. Tian F. Hu J. Zheng P. Zhu W. Design, synthesis and biological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing pyridazinone moiety as c-met inhibitors. Molecules 2018 23 7 1543 10.3390/molecules23071543 29949931
    [Google Scholar]
  63. Lindén B.E. Pihlavisto M. Szatmári I. Otwinowski Z. Smith D.J. Lázár L. Fülöp F. Salminen T.A. Novel pyridazinone inhibitors for vascular adhesion protein-1 (VAP-1): Old target-new inhibition mode. J. Med. Chem. 2013 56 24 9837 9848 10.1021/jm401372d 24304424
    [Google Scholar]
  64. Strappaghetti G. Barbaro R. Marucci G. Synthesis and a1-antagonist activity of derivatives of 4-chloro-5-{4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl}-3(2h)-pyridazinone. Eur. J. Med. Chem. 2000 35 773 779 10.1016/S0223‑5234(00)00161‑6 10960194
    [Google Scholar]
  65. Barbaro R. Betti L. Botta M. Corelli F. Giannaccini G. Maccari L. Manetti F. Strappaghetti G. Corsano S. Synthesis, biological evaluation, and pharmacophore generation of new pyridazinone derivatives with affinity toward α(1)- and α(2)-adrenoceptors. J. Med. Chem. 2001 44 13 2118 2132 10.1021/jm010821u 11405649
    [Google Scholar]
  66. Bender S.M. Wiatrak B. Szczukowski Ł. Świątek P. Rutkowska M. Dzimira S. Merwid-Ląd A. Danielewski M. Szeląg A. Novel 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone exert antinociceptive activity in the tail-flick and formalin test in rodents and reveal reduced gastrotoxicity. Int. J. Mol. Sci. 2020 21 24 9685 10.3390/ijms21249685 33353118
    [Google Scholar]
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