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2000
Volume 21, Issue 8
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

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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References

  1. DubeyS. BhosleP.A. Pyridazinone: An important element of pharmacophore possessing broad spectrum of activity.Med. Chem. Res.201524103579359810.1007/s00044‑015‑1398‑5
    [Google Scholar]
  2. GatesC.A. BackosD.S. ReiganP. NataleN.R. The lateral metalation of isoxazolo[3,4-d]pyridazinones towards hit-to-lead development of selective positive modulators of metabotropic glutamate receptors.Molecules20232819680010.3390/molecules2819680037836643
    [Google Scholar]
  3. SainiM. MehtaK.D. DasR. SainiG. Recent advances in anti-inflammatory potential of pyridazinone derivatives.Mini Rev. Med. Chem.20161612996101210.2174/138955751666616061101581527290912
    [Google Scholar]
  4. TanO.U. SariO.K. Azolo[d]pyridazinones in medicinal chemistry.Future Med. Chem.202113328731110.4155/fmc‑2020‑023433275029
    [Google Scholar]
  5. SinghJ. SharmaD. BansalR. Pyridazinone: An attractive lead for anti-inflammatory and analgesic drug discovery.Future Med. Chem.2017919512710.4155/fmc‑2016‑019427957866
    [Google Scholar]
  6. HassanM.S.A. AhmedE.M. MalahE.A.A. KassabA.E. Anti‐inflammatory activity of pyridazinones: A review.Arch. Pharm. (Weinheim)20223558220006710.1002/ardp.20220006735532263
    [Google Scholar]
  7. RosaF.A. JacominiA.P. Vieira da SilvaM.J. PianoskiK.E. PolettoJ. FranciscoC.B. de Souza FernandesC. MartinelliV. PontesR.M. BackD.F. MouraS. BassoE.A. Controlled pyrazole-hydrazone annulation: Regiodivergent synthesis of 1 H - and 2 H -Pyrazolo[3,4- d]pyridazinones.J. Org. Chem.20238815111401114910.1021/acs.joc.3c0111737463494
    [Google Scholar]
  8. ZhuZ. TangJ. KyriazakosS. KniebA. XuY. ZhangC. PrakashG.K.S. Mono- and difluoromethylation of 3(2 H)-.Pyridazinones. Org. Lett.202426388106810910.1021/acs.orglett.4c03002
    [Google Scholar]
  9. AsifM. A mini review on biological activities of pyridazinone derivatives as antiulcer, antisecretory, antihistamine and particularly against histamine H3R.Mini Rev. Med. Chem.201514131093110310.2174/138955751466614112714313325429662
    [Google Scholar]
  10. PathakS. JainS. PratapA. A review on synthesis and biological potential of dihydropyridines.Lett. Drug Des. Discov.2024211153310.2174/1570180820666230508100955
    [Google Scholar]
  11. PathakS. PandeyR. AgrawalN. Anilinopyrimidines: A review exploring synthetic approaches and biological activity.Lett. Org. Chem.2023201093194410.2174/1570178620666230525140626
    [Google Scholar]
  12. AgrawalN. MishraR. PathakS. GoyalA. ShahK. Hydrazides and hydrazones: Robust scaffolds in neurological and neurodegenerative disorders.Lett. Org. Chem.202320212313610.2174/1570178619666220831122614
    [Google Scholar]
  13. PathakS. SharmaR. A comprehensive review on the benzimidazole scaffold as a potential nucleus for anticancer activity.Lett. Org. Chem.202320980281710.2174/1570178620666230330105103
    [Google Scholar]
  14. PathakS. AgrawalN. GaurS. A review on diverse biological activity of heterocyclic nucleus pyrazine and its derivatives: A key for the researchers.Lett. Org. Chem.202421435136110.2174/0115701786273932230927062616
    [Google Scholar]
  15. AgrawalN. BansalD. PathakS. Exploring the therapeutic marvels: A comprehensive review on the biological potential of quinoline-5,8-dione.Med. Chem.202420438539610.2174/011573406428767723121507081638173200
    [Google Scholar]
  16. AgrawalN. GoswamiR. PathakS. Synthetic methods for various chromeno-fused heterocycles and their potential as antimicrobial agents.Med. Chem.202420211512910.2174/011573406427474823100507410037855281
    [Google Scholar]
  17. SabnisR.W. Novel pyridazinones as TRPC5 inhibitors for treating kidney diseases.ACS Med. Chem. Lett.202112452652710.1021/acsmedchemlett.1c0012333859787
    [Google Scholar]
  18. CantiniN. SchepetkinI.A. DanilenkoN.V. KhlebnikovA.I. CrocettiL. GiovannoniM.P. KirpotinaL.N. QuinnM.T. Pyridazinones and structurally related derivatives with anti-inflammatory activity.Molecules20222712374910.3390/molecules2712374935744876
    [Google Scholar]
  19. AkhtarW. ShaquiquzzamanM. AkhterM. VermaG. KhanM.F. AlamM.M. The therapeutic journey of pyridazinone.Eur. J. Med. Chem.201612325628110.1016/j.ejmech.2016.07.06127484513
    [Google Scholar]
  20. AbouzidK. BekhitS.A. Novel anti-inflammatory agents based on pyridazinone scaffold; design, synthesis and in vivo activity.Bioorg. Med. Chem.200816105547555610.1016/j.bmc.2008.04.00718430576
    [Google Scholar]
  21. CombsD.W. RampullaM.S. DemersJ.P. FaloticoR. MooreJ.B. Heteroatom analogs of bemoradan: Chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones.J. Med. Chem.199235117217610.1021/jm00079a0231732525
    [Google Scholar]
  22. RobertsonD.W. LeanderJ.D. LawsonR. BeedleE.E. ClarkC.R. PottsB.D. ParliC.J. Discovery and anticonvulsant activity of the potent metabolic inhibitor 4-amino-N-(2,6-dimethylphenyl)-3,5-dimethylbenzamide.J. Med. Chem.198730101742174610.1021/jm00393a0103656350
    [Google Scholar]
  23. ArchanS. TollerW. Levosimendan: Current status and future prospects.Curr. Opin. Anaesthesiol.2008211788410.1097/ACO.0b013e3282f357a518195615
    [Google Scholar]
  24. AvcıD. BahçeliS. TamerÖ. AtalayY. 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.201593101147115610.1139/cjc‑2015‑0176
    [Google Scholar]
  25. AsifM. Overview on emorfazone and other related 3(2H) pyridazinone analogues displaying analgesic and anti- inflammatory activity mohammad.Ann. Med. Chem. Res.2015319
    [Google Scholar]
  26. UkenaD. RentzK. ReiberC. SybrechtG.W. Effects of the mixed phosphodiesterase III/IV inhibitor, zardaverine, on airway function in patients with chronic airflow obstruction.Respir. Med.199589644144410.1016/0954‑6111(95)90214‑77644776
    [Google Scholar]
  27. IbrahimH.M. BehbehaniH. ElnagdiM.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.20137112310.1186/1752‑153X‑7‑12323867062
    [Google Scholar]
  28. AbbasS.H. RahmaA.G.E.D.A.A. AzizA.M. AlyO.M. BeshrE.A. EldeenG.A.M. Synthesis, cytotoxic activity, and tubulin polymerization inhibitory activity of new pyrrol-2(3H)-ones and pyridazin-3(2H)-ones.Bioorg. Chem.201666466210.1016/j.bioorg.2016.03.00727016713
    [Google Scholar]
  29. ZhangX. LuoJ. LiQ. XinQ. YeL. ZhuQ. ShiZ. ZhanF. ChuB. LiuZ. JiangY. 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.202122611381210.1016/j.ejmech.2021.11381234536673
    [Google Scholar]
  30. AhmedE.M. KassabA.E. MalahE.A.A. HassanM.S.A. Synthesis and biological evaluation of pyridazinone derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents.Eur. J. Med. Chem.2019171253710.1016/j.ejmech.2019.03.03630904755
    [Google Scholar]
  31. BarberotC. MoniotA. SimonA.I. MalleretL. YegorovaT. CochardL.M. BentaherA. MédebielleM. BouillonJ.P. HénonE. SapiJ. VelardF. GérardS. Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents.Eur. J. Med. Chem.201814613914610.1016/j.ejmech.2018.01.03529407945
    [Google Scholar]
  32. BashirR. YaseenS. OvaisS. AhmadS. HamidH. AlamM.S. SamimM. JavedK. Synthesis and biological evaluation of some novel sulfamoylphenyl-pyridazinone as anti-inflammatory agents (Part-II).J. Enzyme Inhib. Med. Chem.2012271929610.3109/14756366.2011.57703621612377
    [Google Scholar]
  33. GökçeM. FethiM. ¸ahinS. KüpeliE. Yes¸iladaE.Y. Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives.Arzneimittelforschung2004547396401
    [Google Scholar]
  34. HusainA. DrabuS. KumarN. AlamM.M. AhmadA. Synthesis and biological evaluation of some new pyridazinone derivatives.J. Enzyme Inhib. Med. Chem.201126574274810.3109/14756366.2010.54881021271866
    [Google Scholar]
  35. LokshaY.M. AlhaseebA.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.20203533190029510.1002/ardp.20190029531944384
    [Google Scholar]
  36. KilicB. ErdoganM. GulcanH.O. AksakalF. OrukluN. BagriacikE.U. DogruerD.S. Design, synthesis and investigation of new diphenyl substituted pyridazinone derivatives as both cholinesterase and Aβ-aggregation inhibitors.Med. Chem.2019151597610.2174/157340641466618052407324129792155
    [Google Scholar]
  37. PauA. CattoM. PinnaG. FrauS. MurinedduG. AsproniB. CurzuM.M. PisaniL. LeonettiF. LozaM.I. BreaJ. PinnaG.A. CarottiA. Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors.ChemMedChem20151061054107010.1002/cmdc.20150012425924828
    [Google Scholar]
  38. LiuY. JinS. PengX. LuD. ZengL. SunY. AiJ. GengM. HuY. Pyridazinone derivatives displaying highly potent and selective inhibitory activities against c-Met tyrosine kinase.Eur. J. Med. Chem.201610832233310.1016/j.ejmech.2015.11.04226698536
    [Google Scholar]
  39. ÇeçenM. OhJ.M. ÖzdemirZ. BüyüktuncelS.E. UysalM. AbdelgawadM.A. MusaA. GambacortaN. NicolottiO. MathewB. KimH. Design, synthesis, and biological evaluation of pyridazinones containing the (2-fluorophenyl) piperazine moiety as selective mao-b inhibitors.Molecules20202522537110.3390/molecules2522537133212876
    [Google Scholar]
  40. OvaisS. JavedK. YaseenS. BashirR. RathoreP. YaseenR. HameedA.D. SamimM. 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.20136735235810.1016/j.ejmech.2013.06.05023887055
    [Google Scholar]
  41. AbubshaitS.A. An efficient synthesis and reactions of novel indolyl-pyridazinone derivatives with expected biological activity.Molecules20071212542
    [Google Scholar]
  42. AbouzidK. HakeemA.M. KhalilO. MakladY. Pyridazinone derivatives: Design, synthesis, and in vitro vasorelaxant activity.Bioorg. Med. Chem.200816138238910.1016/j.bmc.2007.09.03117905589
    [Google Scholar]
  43. RahmanA.H.M. AzizA.M. TinsleyH.N. GaryB.D. CanzoneriJ.C. PiazzaG.A. Design and synthesis of substituted pyridazinone‐1‐acetylhydrazones as novel phosphodiesterase 4 inhibitors.Arch. Pharm. (Weinheim)2016349210411110.1002/ardp.20150036326686665
    [Google Scholar]
  44. BiaginiP. BiancalaniC. GrazianoA. CesariN. GiovannoniM.P. CilibrizziA. PiazV.D. VergelliC. CrocettiL. DelcanaleM. ArmaniE. RizziA. PucciniP. GalloP.M. SpinabelliD. CarusoP. Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity.Bioorg. Med. Chem.201018103506351710.1016/j.bmc.2010.03.06620413313
    [Google Scholar]
  45. GràciaJ. BuilM.A. CastroJ. EichhornP. FerrerM. GavaldàA. HernándezB. SegarraV. LehnerM.D. MorenoI. PagèsL. RobertsR.S. SerratJ. SevillaS. TaltavullJ. AndrésM. CabedoJ. VilellaD. CalamaE. CarcasonaC. MiralpeixM. Biphenyl pyridazinone derivatives as inhaled pde4 inhibitors: Structural biology and structure-activity relationships.J. Med. Chem.20165923104791049710.1021/acs.jmedchem.6b0082927933955
    [Google Scholar]
  46. SimonA.I. MoniotA. BisiN. VargasP.M. AudonnetS. CochardL.M. SapiJ. HénonE. VelardF. GérardS. Pyridazinone derivatives as potential anti-inflammatory agents: Synthesis and biological evaluation as PDE4 inhibitors.RSC Med. Chem.202112458459210.1039/D0MD00423E34046629
    [Google Scholar]
  47. AminE.N. AlimA.A.A.M. MotyA.S.G. ShorbagiE.A.N.A. RahmanA.M.S. Synthesis of new 4,5-3(2H)pyridazinone derivatives and their cardiotonic, hypotensive, and platelet aggregation inhibition activities.Arch. Pharm. Res.2010331254610.1007/s12272‑010‑2222‑x20191341
    [Google Scholar]
  48. CostasT. LagoC.M.C. VilaN. BesadaP. CanoE. TeránC. New platelet aggregation inhibitors based on pyridazinone moiety.Eur. J. Med. Chem.20159411312210.1016/j.ejmech.2015.02.06125757094
    [Google Scholar]
  49. BesadaP. ViñaD. CostasT. LagoC.M.C. VilaN. TeránT.I. SturleseM. MoroS. TeránC. Pyridazinones containing dithiocarbamoyl moieties as a new class of selective MAO-B inhibitors.Bioorg. Chem.202111510520310.1016/j.bioorg.2021.10520334371375
    [Google Scholar]
  50. ÖzdemirZ. AlagözM.A. UsluH. KarakurtA. ErikciA. UcarG. UysalM. Synthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitors.Pharmacol. Rep.202072369270410.1007/s43440‑020‑00070‑w32144745
    [Google Scholar]
  51. SukurogluM. OnkolT. OnurdağF.K. AkalınG. ŞahinM.F. Synthesis and in vitro biological activity of new 4,6-disubstituted 3(2H)-pyridazinone-acetohydrazide derivatives.Z. Naturforsch. C J. Biosci.2012675-625726510.1515/znc‑2012‑5‑60422888530
    [Google Scholar]
  52. AbdelbasetM.S. RahmaA.G.E.D.A. AbdelrahmanM.H. RamadanM. YoussifB.G.M. BukhariS.N.A. MohamedM.F.A. AzizA.M. Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors.Bioorg. Chem.20188015116310.1016/j.bioorg.2018.06.00329920422
    [Google Scholar]
  53. WuX. DaiM. CuiR. WangY. LiC. PengX. ZhaoJ. WangB. DaiY. FengD. YangT. JiangH. GengM. AiJ. ZhengM. LiuH. Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyridazinone derivatives as covalent FGFR inhibitors.Acta Pharm. Sin. B202111378179410.1016/j.apsb.2020.09.00233777682
    [Google Scholar]
  54. MurinedduG. CignarellaG. ChelucciG. LorigaG. PinnaG.A. Synthesis and cytotoxic activities of pyrrole [2, 3-d] pyridazin-4-one derivatives.Chem. pharm. bul200250(6)754759
    [Google Scholar]
  55. GutierrezD.A. DeJesusR.E. ContrerasL. PalomaresR.I.A. VillanuevaP.J. BalderramaK.S. MonterrozaL. LarragoityM. RamirezV.A. AguileraR.J. A new pyridazinone exhibits potent cytotoxicity on human cancer cells via apoptosis and poly-ubiquitinated protein accumulation.Cell Biol. Toxicol.201935650351910.1007/s10565‑019‑09466‑830825052
    [Google Scholar]
  56. KrasavinM. ShetnevA. BaykovS. KalininS. NocentiniA. SharoykoV. PoliG. TuccinardiT. KorsakovM. TennikovaT.B. SupuranC.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.201916830131410.1016/j.ejmech.2019.02.04430826507
    [Google Scholar]
  57. AlagözM.A. ÖzdemirZ. UysalM. CarradoriS. GalloriniM. RicciA. ZaraS. MathewB. Synthesis, cytotoxicity and anti-proliferative activity against ags cells of new 3(2H)-pyridazinone derivatives endowed with a piperazinyl linker.Pharmaceuticals202114318310.3390/ph1403018333668893
    [Google Scholar]
  58. BenderS.M. WiatrakB. DzimiraS. Merwid-LądA. SzczukowskiŁ. ŚwiątekP. SzelągA. 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.20222317989710.3390/ijms2317989736077306
    [Google Scholar]
  59. SinghJ. SainiV. KumarA. BansalR. 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.20177120121010.1016/j.bioorg.2017.02.00628236449
    [Google Scholar]
  60. KimE.Y. KangS.T. JungH. ParkC.H. YunC.S. HwangJ.Y. ByunB.J. LeeC.O. KimH.R. HaJ.D. RyuD.H. ChoS.Y. Discovery of substituted pyrazol-4-yl pyridazinone derivatives as novel c-Met kinase inhibitors.Arch. Pharm. Res.201639445346410.1007/s12272‑015‑0703‑726753914
    [Google Scholar]
  61. LuD. YanJ. WangL. LiuH. ZengL. ZhangM. DuanW. JiY. CaoJ. GengM. ShenA. HuY. Design, synthesis, and biological evaluation of the first c-met/hdac inhibitors based on pyridazinone derivatives.ACS Med. Chem. Lett.20178883083410.1021/acsmedchemlett.7b0017228835797
    [Google Scholar]
  62. LiuX. KouJ. XiaoZ. TianF. HuJ. ZhengP. ZhuW. Design, synthesis and biological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing pyridazinone moiety as c-met inhibitors.Molecules2018237154310.3390/molecules2307154329949931
    [Google Scholar]
  63. LindénB.E. PihlavistoM. SzatmáriI. OtwinowskiZ. SmithD.J. LázárL. FülöpF. SalminenT.A. Novel pyridazinone inhibitors for vascular adhesion protein-1 (VAP-1): Old target-new inhibition mode.J. Med. Chem.201356249837984810.1021/jm401372d24304424
    [Google Scholar]
  64. StrappaghettiG. BarbaroR. MarucciG. 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.20003577377910.1016/S0223‑5234(00)00161‑610960194
    [Google Scholar]
  65. BarbaroR. BettiL. BottaM. CorelliF. GiannacciniG. MaccariL. ManettiF. StrappaghettiG. CorsanoS. Synthesis, biological evaluation, and pharmacophore generation of new pyridazinone derivatives with affinity toward α(1)- and α(2)-adrenoceptors.J. Med. Chem.200144132118213210.1021/jm010821u11405649
    [Google Scholar]
  66. BenderS.M. WiatrakB. SzczukowskiŁ. ŚwiątekP. RutkowskaM. DzimiraS. Merwid-LądA. DanielewskiM. SzelągA. 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.20202124968510.3390/ijms2124968533353118
    [Google Scholar]
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