Skip to content
2000
image of An Overview of Pyridazine Derivatives: Various Approaches to Synthesis, Reactivity, and Biological Activity

Abstract

Pyridazine derivatives have garnered considerable attention due to their remarkable chemical reactivity and extensive biological applications. This study presents a comprehensive review of recent advancements in the synthesis of pyridazine derivatives, with a focus on both conventional and innovative approaches ( microwave and sonication), which include cyclocondensation, cycloaddition, addition, transition metal-catalyzed reactions, ring-opening and closure, coupling, nucleophilic cyclization, Knoevenagel condensation, hydrogenation, oxidation, aldol condensation, Diels-Alder, acylation, bromination, lithiation, and acid hydrolysis reactions. The distinctive characteristics of the pyridazine ring enhance its versatility in chemical reactions, facilitating its utilization in the synthesis of pharmacologically active compounds. Furthermore, the reactivity patterns are clearly delineated, emphasizing changes in functional groups and ring fusion strategies. This study examines the significant biological potential of pyridazine derivatives, encompassing antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, antioxidant, antidiabetic, anticoagulant, analgesic, and cardiovascular properties. It aims to guide future research by identifying appealing structural motifs and synthesis pathways that may lead to the development of innovative medicinal molecules.

Loading

Article metrics loading...

/content/journals/mroc/10.2174/0118756298421529251030163718
2026-01-12
2026-01-31
Loading full text...

Full text loading...

References

  1. Dekhane D.V. Pawar S.S. Gupta S. Shingare M.S. Patil C.R. Thore S.N. Synthesis and anti-inflammatory activity of some new 4,5-dihydro-1,5-diaryl-1H-pyrazole-3-substituted-heteroazole derivatives. Bioorg. Med. Chem. Lett. 2011 21 21 6527 6532 10.1016/j.bmcl.2011.08.061 21958541
    [Google Scholar]
  2. Abd El-Hameed R.H. Mahgoub S. El-Shanbaky H.M. Mohamed M.S. Ali S.A. Utility of novel 2-furanones in synthesis of other heterocyclic compounds having anti-inflammatory activity with dual COX2/LOX inhibition. J. Enzyme Inhib. Med. Chem. 2021 36 1 977 986 10.1080/14756366.2021.1908277 33957835
    [Google Scholar]
  3. Sharma D. Bansal R. Synthesis of 2-substituted-4-aryl-6-phenylpyridazin-3(2H)-ones as potential anti-inflammatory and analgesic agents with cardioprotective and ulcerogenic sparing effects. Med. Chem. Res. 2016 25 8 1574 1589 10.1007/s00044‑016‑1588‑9
    [Google Scholar]
  4. Ünsal-Tan O. Özden K. Rauk A. Balkan A. Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones. Eur. J. Med. Chem. 2010 45 6 2345 2352 10.1016/j.ejmech.2010.02.012 20207453
    [Google Scholar]
  5. Ahmed E.M. Kassab A.E. El-Malah 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]
  6. Li C.S. Brideau C. Chan C.C. Savoie C. Claveau D. Charleson S. Gordon R. Greig G. Gauthier J.Y. Lau C.K. Riendeau D. Thérien M. Wong E. Prasit P. Pyridazinones as selective cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. Lett. 2003 13 4 597 600 10.1016/S0960‑894X(02)01045‑4 12639538
    [Google Scholar]
  7. Badawi W.A. Rashed M. Nocentini A. Bonardi A. Abd-Alhaseeb M.M. Al-Rashood S.T. Veerakanellore G.B. Majrashi T.A. Elkaeed E.B. Elgendy B. Gratteri P. Supuran C.T. Eldehna W.M. Elagawany M. Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: Synthesis, biological evaluations and modelling insights. J. Enzyme Inhib. Med. Chem. 2023 38 1 2201407 10.1080/14756366.2023.2201407 37078173
    [Google Scholar]
  8. Ahmed E.M. Hassan M.S.A. El-Malah A.A. Kassab A.E. New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation. Bioorg. Chem. 2020 95 103497 10.1016/j.bioorg.2019.103497 31838289
    [Google Scholar]
  9. Ghareb N. Elshihawy H.A. Abdel-Daim M.M. Helal M.A. Novel pyrazoles and pyrazolo[1,2- a]pyridazines as selective COX-2 inhibitors; Ultrasound-assisted synthesis, biological evaluation, and DFT calculations. Bioorg. Med. Chem. Lett. 2017 27 11 2377 2383 10.1016/j.bmcl.2017.04.020 28427813
    [Google Scholar]
  10. Chintakunta V.K. Akella V. Vedula M.S. Mamnoor P.K. Mishra P. Casturi S.R. Vangoori A. Rajagopalan R. 3-O-Substituted benzyl pyridazinone derivatives as COX inhibitors. Eur. J. Med. Chem. 2002 37 4 339 347 10.1016/S0223‑5234(02)01336‑3 11960669
    [Google Scholar]
  11. Szczukowski Ł. Krzyżak E. Zborowska A. Zając P. Potyrak K. Peregrym K. Wiatrak B. Marciniak A. Świątek P. Design, synthesis and comprehensive investigations of pyrrolo[3,4-d]pyridazinone-based 1,3,4-oxadiazole as new class of selective COX-2 inhibitors. Int. J. Mol. Sci. 2020 21 24 9623 10.3390/ijms21249623 33348757
    [Google Scholar]
  12. Szczukowski Ł. Redzicka A. Wiatrak B. Krzyżak E. Marciniak A. Gębczak K. Gębarowski T. Świątek P. Design, synthesis, biological evaluation and in silico studies of novel pyrrolo[3,4-d]pyridazinone derivatives with promising anti-inflammatory and antioxidant activity. Bioorg. Chem. 2020 102 104035 10.1016/j.bioorg.2020.104035 32721780
    [Google Scholar]
  13. Rao P. Knaus E.E. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): Cyclooxygenase (COX) inhibition and beyond. J. Pharm. Pharm. Sci. 2008 11 2 81s 110s 10.18433/J3T886
    [Google Scholar]
  14. Szczukowski Ł. Krzyżak E. Wiatrak B. Jawień P. Marciniak A. Kotynia A. Świątek P. New N-Substituted-1,2,4-triazole Derivatives of Pyrrolo[3,4-d]pyridazinone with significant anti-inflammatory activity—design, synthesis and complementary in vitro, computational and spectroscopic studies. Int. J. Mol. Sci. 2021 22 20 11235 10.3390/ijms222011235 34681894
    [Google Scholar]
  15. 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]
  16. Saeed M.M. Khalil N.A. Ahmed E.M. Eissa K.I. Synthesis and anti-inflammatory activity of novel pyridazine and pyridazinone derivatives as non-ulcerogenic agents. Arch. Pharm. Res. 2012 35 12 2077 2092 10.1007/s12272‑012‑1205‑5 23263802
    [Google Scholar]
  17. Cignarella G. Loriga M. Pinna G.A. Pirisi M.A. Schiatti P. Selva D. [Unexpected anti-inflammatory activity of rigid structures derived from antihypertensive 6-arylpyridazinones. III. Synthesis and activity of 7-fluoro- and 5-keto-5H-indeno(1,2-c)pyridozines]. Farmaco, Sci. 1982 37 2 133 144 7067808
    [Google Scholar]
  18. Zaoui Y. Ramli Y. Tan S.L. Tiekink E.R.T. Chemlal L. Mague J.T. Taoufik J. Faouzi M.E.A. Ansar M.H. Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase. J. Mol. Struct. 2021 1234 130177 10.1016/j.molstruc.2021.130177
    [Google Scholar]
  19. Van der Mey M. Bommelé K.M. Boss H. Hatzelmann A. Van Slingerland M. Sterk G.J. Timmerman H. Synthesis and structure-activity relationships of cis-tetrahydrophthalazinone/pyridazinone hybrids: A novel series of potent dual PDE3/PDE4 inhibitory agents. J. Med. Chem. 2003 46 10 2008 2016 10.1021/jm030776l 12723963
    [Google Scholar]
  20. Abou-Seri S.M. Eldehna W.M. Ali M.M. Abou El Ella D.A. 1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation. Eur. J. Med. Chem. 2016 107 165 179 10.1016/j.ejmech.2015.10.053 26590508
    [Google Scholar]
  21. Boraei A.T.A. Ashour H.K. El Tamany E.S.H. Abdelmoaty N. El-Falouji A.I. Gomaa M.S. Design and synthesis of new phthalazine-based derivatives as potential EGFR inhibitors for the treatment of hepatocellular carcinoma. Bioorg. Chem. 2019 85 293 307 10.1016/j.bioorg.2018.12.039 30654221
    [Google Scholar]
  22. Ahmed M.F. Santali E.Y. Mohi El-Deen E.M. Naguib I.A. El-Haggar R. Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation, and molecular modeling studies. Bioorg. Chem. 2021 106 104473 10.1016/j.bioorg.2020.104473 33243490
    [Google Scholar]
  23. He Z.X. Gong Y.P. Zhang X. Ma L.Y. Zhao W. Pyridazine as a privileged structure: An updated review on anticancer activity of pyridazine containing bioactive molecules. Eur. J. Med. Chem. 2021 209 112946 10.1016/j.ejmech.2020.112946 33129590
    [Google Scholar]
  24. Eldehna W.M. Ibrahim H.S. Abdel-Aziz H.A. Farrag N.N. Youssef M.M. Design, synthesis and in vitro antitumor activity of novel N-substituted-4-phenyl/benzylphthalazin-1-ones. Eur. J. Med. Chem. 2015 89 549 560 10.1016/j.ejmech.2014.10.064 25462265
    [Google Scholar]
  25. Atmaca H. Ilhan S. Çamli Pulat Ç. Dundar B.A. Zora M. Evaluation of novel spiro-pyrrolopyridazine derivatives as anticancer compounds: In vitro selective cytotoxicity, induction of apoptosis, egfr inhibitory activity, and molecular docking analysis. ACS Omega 2024 9 22 23713 23723 10.1021/acsomega.4c00794 38854531
    [Google Scholar]
  26. Eldehna W.M. Abou-Seri S.M. El Kerdawy A.M. Ayyad R.R. Hamdy A.M. Ghabbour H.A. Ali M.M.A. Abou El Ella D.A. Increasing the binding affinity of VEGFR-2 inhibitors by extending their hydrophobic interaction with the active site: Design, synthesis and biological evaluation of 1-substituted-4-(4-methoxybenzyl)phthalazine derivatives. Eur. J. Med. Chem. 2016 113 50 62 10.1016/j.ejmech.2016.02.029 26922228
    [Google Scholar]
  27. Abdelbaset M.S. Abuo-Rahma G.E.D.A. Abdelrahman M.H. Ramadan M. Youssif B.G.M. Bukhari S.N.A. Mohamed M.F.A. Abdel-Aziz 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]
  28. 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]
  29. George R.F. Fouad M.A. Gomaa I.E.O. Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers. Eur. J. Med. Chem. 2016 112 48 59 10.1016/j.ejmech.2016.01.048 26874744
    [Google Scholar]
  30. Rathish I.G. Javed K. Ahmad S. Bano S. Alam M.S. Akhter M. Pillai K.K. Ovais S. Samim M. Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones. Eur. J. Med. Chem. 2012 49 304 309 10.1016/j.ejmech.2012.01.026 22305543
    [Google Scholar]
  31. Abbas S.H. Abuo-Rahma G.E.D.A.A. Abdel-Aziz M. Aly O.M. Beshr E.A. Gamal-Eldeen 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]
  32. Gutierrez D.A. DeJesus R.E. Contreras L. Rodriguez-Palomares I.A. Villanueva P.J. Balderrama K.S. Monterroza L. Larragoity M. Varela-Ramirez 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]
  33. Sawant A.S.S.S.K. Hese S.V. Pisal P.M. Sawant S.S. Kamble V.A. Kamble V.T. Gacche R.N. Synthesis and evaluation of novel 4-chloro-5-(cyclic/acyclic amino)-2-p-tolyl(2H)-pyridazin-3-one derivatives as anticancer, antiangiogenic, and antioxidant agents. Chem. Biol. Interact. 2020 10 5 128 139
    [Google Scholar]
  34. El-Nagar M.K.S. Shahin M.I. El-Behairy M.F. Taher E.S. El-Badawy M.F. Sharaky M. Abou El Ella D.A. Abouzid K.A.M. Adel M. Pyridazinone-based derivatives as anticancer agents endowed with anti-microbial activity: Molecular design, synthesis, and biological investigation. RSC Med. Chem. 2024 15 10 3529 3557 10.1039/D4MD00481G 39246752
    [Google Scholar]
  35. Hashem H.E. Haneen D.S.A. Saied K.F. Youssef A.S.A. Synthesis of new annulated pyridazine derivatives and studying their antioxidant and antimicrobial activities. Synth. Commun. 2019 49 22 3169 3180 10.1080/00397911.2019.1658786
    [Google Scholar]
  36. Chen S. Zhang M. Feng S. Gong C. Zhou Y. Xing L. He B. Wu Y. Xue W. Design, synthesis and biological activity of chalcone derivatives containing pyridazine. Arab. J. Chem. 2023 16 7 104852 10.1016/j.arabjc.2023.104852
    [Google Scholar]
  37. Mohamed N.R. El-Saidi M.M.T. Ali Y.M. Elnagdi M.H. Microwaves in organic synthesis: Facile synthesis of biologically active pyridazinone and iminopyridazine derivatives. J. Heterocycl. Chem. 2007 44 6 1333 1337 10.1002/jhet.5570440615
    [Google Scholar]
  38. Cui Z.M. Zhou B.H. Fu C. Chen L. Fu J. Cao F.J. Yang X.J. Zhou L. Simple analogues of quaternary benzo[ c]phenanthridine alkaloids: Discovery of a novel antifungal 2-phenylphthalazin-2-ium scaffold with excellent potency against phytopathogenic fungi. J. Agric. Food Chem. 2020 68 52 15418 15427 10.1021/acs.jafc.0c06507 33332120
    [Google Scholar]
  39. Coelho A. Raviña E. Fraiz N. Yáñez M. Laguna R. Cano E. Sotelo E. Design, synthesis, and structure-activity relationships of a novel series of 5-alkylidenepyridazin-3(2H)-ones with a non-cAMP-based antiplatelet activity. J. Med. Chem. 2007 50 26 6476 6484 10.1021/jm061401d 18031002
    [Google Scholar]
  40. Costas T. Costas-Lago 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]
  41. Costas T. Besada P. Piras A. Acevedo L. Yañez M. Orallo F. Laguna R. Terán C. New pyridazinone derivatives with vasorelaxant and platelet antiaggregatory activities. Bioorg. Med. Chem. Lett. 2010 20 22 6624 6627 10.1016/j.bmcl.2010.09.031 20880705
    [Google Scholar]
  42. Amin E.N. Abdel-Alim A.A.M. Abdel-Moty S.G. El-Shorbagi A.N.A. Abdel-Rahman 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]
  43. Thyes M. Lehmann H.D. Gries J. Koenig H. Kretzschmar R. Kunze J. Lebkuecher R. Lenke D. 6-Aryl-4,5-dihydro-3(2H)-pyridazinones. A new class of compounds with platelet aggregation inhibiting and hypotensive activities. J. Med. Chem. 1983 26 6 800 807 10.1021/jm00360a004 6854582
    [Google Scholar]
  44. Meyers C. Yáñez M. Elmaatougi A. Verhelst T. Coelho A. Fraiz N. Lemière G.L.F. Garcı’a-Mera X. Laguna R. Cano E. Maes B.U.W. Sotelo E. 2-Substituted 4-, 5-, and 6-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones and 2-substituted 4,5-bis[(1E)-3-oxo-3-phenylprop-1-en-1-yl]pyridazin-3(2H)-ones as potent platelet aggregation inhibitors: Design, synthesis, and SAR studies. Bioorg. Med. Chem. Lett. 2008 18 2 793 797 10.1016/j.bmcl.2007.11.034 18053717
    [Google Scholar]
  45. Estevez I. Raviña E. Sotelo E. Pyridazines. XV. Synthesis of 6‐aryl‐5‐amino‐3(2 H)‐pyridazinones as potential platelet aggregation inhibitors. J. Heterocycl. Chem. 1998 35 6 1421 1428 10.1002/jhet.5570350634
    [Google Scholar]
  46. Piaz V.D. Ciciani G. Turco G. Giovannoni M.P. Miceli M. Pirisino R. Perretti M. 5-Acyl-6-aryl-4-nitro-3(2H)pyridazinones and related 4-amino compounds: Synthesis and pharmacological evaluation. J. Pharm. Sci. 1991 80 4 341 348 10.1002/jps.2600800412 1865334
    [Google Scholar]
  47. Van der Mey M. Hatzelmann A. Van Klink G.P.M. Van der Laan I.J. Sterk G.J. Thibaut U. Ulrich W.R. Timmerman H. Novel selective PDE4 inhibitors. 2. Synthesis and structure-activity relationships of 4-aryl-substituted cis-tetra- and cis-hexahydrophthalazinones. J. Med. Chem. 2001 44 16 2523 2535 10.1021/jm010838c 11472206
    [Google Scholar]
  48. Salado I.G. Singh A.K. Moreno-Cinos C. Sakaine G. Siderius M. Van der Veken P. Matheeussen A. van der Meer T. Sadek P. Gul S. Maes L. Sterk G.J. Leurs R. Brown D. Augustyns K. Lead optimization of phthalazinone phosphodiesterase inhibitors as novel antitrypanosomal compounds. J. Med. Chem. 2020 63 7 3485 3507 10.1021/acs.jmedchem.9b00985 32196340
    [Google Scholar]
  49. Blaazer A.R. Singh A.K. de Heuvel E. Edink E. Orrling K.M. Veerman J.J.N. van den Bergh T. Jansen C. Balasubramaniam E. Mooij W.J. Custers H. Sijm M. Tagoe D.N.A. Kalejaiye T.D. Munday J.C. Tenor H. Matheeussen A. Wijtmans M. Siderius M. de Graaf C. Maes L. de Koning H.P. Bailey D.S. Sterk G.J. de Esch I.J.P. Brown D.G. Leurs R. Targeting a subpocket in Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) enables the structure-based discovery of selective inhibitors with trypanocidal activity. J. Med. Chem. 2018 61 9 3870 3888 10.1021/acs.jmedchem.7b01670 29672041
    [Google Scholar]
  50. Orrling K.M. Jansen C. Vu X.L. Balmer V. Bregy P. Shanmugham A. England P. Bailey D. Cos P. Maes L. Adams E. van den Bogaart E. Chatelain E. Ioset J.R. van de Stolpe A. Zorg S. Veerman J. Seebeck T. Sterk G.J. de Esch I.J.P. Leurs R. Catechol pyrazolinones as trypanocidals: Fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase B1. J. Med. Chem. 2012 55 20 8745 8756 10.1021/jm301059b 22963052
    [Google Scholar]
  51. Veerman J. van den Bergh T. Orrling K.M. Jansen C. Cos P. Maes L. Chatelain E. Ioset J.R. Edink E.E. Tenor H. Seebeck T. de Esch I. Leurs R. Sterk G.J. Synthesis and evaluation of analogs of the phenylpyridazinone NPD-001 as potent trypanosomal TbrPDEB1 phosphodiesterase inhibitors and in vitro trypanocidals. Bioorg. Med. Chem. 2016 24 7 1573 1581 10.1016/j.bmc.2016.02.032 26935942
    [Google Scholar]
  52. Shahid M. van Amsterdam R.G.M. de Boer J. ten Berge R.E. Nicholson C.D. Zaagsma J. The presence of five cyclic nucleotide phosphodiesterase isoenzyme activities in bovine tracheal smooth muscle and the functional effects of selective inhibitors. Br. J. Pharmacol. 1991 104 2 471 477 10.1111/j.1476‑5381.1991.tb12453.x 1665737
    [Google Scholar]
  53. Bakewell S.J. Coates W.J. Comer M.B. Reeves M.L. Warrington B.H. Inotropic, vasodilator and low Km, cAMP-selective, cGMP-inhibited phosphodiesterase (PDE III) inhibitory activities of 4a-methyl-4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3(2H)-ones and 4a-methyl-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones. Eur. J. Med. Chem. 1990 25 9 765 774 10.1016/0223‑5234(90)90196‑A
    [Google Scholar]
  54. Yamaguchi M. Maruyama N. Koga T. Kamei K. Akima M. Kuroki T. Hamana M. Ohi N. ChemInform Abstract: Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. Part 5. Thienopyridazinone derivatives. ChemInform 1995 26 35
    [Google Scholar]
  55. Yamaguchi M. Maruyama N. Koga T. Kamei K. Akima M. Kuroki T. Hamana M. Ohi N. Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. V. Thienopyridazinone derivatives. Chem. Pharm. Bull. 1995 43 2 236 240
    [Google Scholar]
  56. Yamada T. Shimamura H. Tsukamoto Y. Yamaguchi A. Ohki M. Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives. J. Med. Chem. 1983 26 8 1144 1149 10.1021/jm00362a011 6876082
    [Google Scholar]
  57. Rubat C. Coudert P. Bastide P. Tronche P. Behavioural profile of two potential antidepressant pyridazine derivatives including arylpiperazinyl moieties in their structure, in mice. J. Pharm. Pharmacol. 1995 47 2 162 170 10.1111/j.2042‑7158.1995.tb05771.x 7602473
    [Google Scholar]
  58. Procopiou P.A. Browning C. Buckley J.M. Clark K.L. Fechner L. Gore P.M. Hancock A.P. Hodgson S.T. Holmes D.S. Kranz M. Looker B.E. Morriss K.M.L. Parton D.L. Russell L.J. Slack R.J. Sollis S.L. Vile S. Watts C.J. The discovery of phthalazinone-based human H1 and H3 single-ligand antagonists suitable for intranasal administration for the treatment of allergic rhinitis. J. Med. Chem. 2011 54 7 2183 2195 10.1021/jm1013874 21381763
    [Google Scholar]
  59. Strappaghetti G. Brodi C. Giannaccini G. Betti L. New 4-(4-methyl-phenyl)phthalazin-1(2H)-one derivatives and their effects on α1-receptors. Bioorg. Med. Chem. Lett. 2006 16 10 2575 2579 10.1016/j.bmcl.2006.02.068 16545955
    [Google Scholar]
  60. Tsuji T. Yamaguchi M. Kuroyanagi J. Furuzono S. Konishi M. Terayama K. Tanaka J. Saito M. Kobayashi Y. Discovery of novel pyridazine derivatives as glucose transporter type 4 (GLUT4) translocation activators. Bioorg. Med. Chem. Lett. 2019 29 14 1785 1790 10.1016/j.bmcl.2019.05.013 31101471
    [Google Scholar]
  61. Betti L. Floridi M. Giannaccini G. Manetti F. Strappaghetti G. Tafi A. Botta M. α1-Adrenoceptor antagonists. 5. Pyridazinone-arylpiperazines. Probing the influence on affinity and selectivity of both ortho-Alkoxy groups at the arylpiperazine moiety and cyclic substituents at the pyridazinone nucleus. Bioorg. Med. Chem. Lett. 2003 13 2 171 173 10.1016/S0960‑894X(02)00932‑0 12482417
    [Google Scholar]
  62. Demirayak S. Karaburun A.C. Beis R. Some pyrrole substituted aryl pyridazinone and phthalazinone derivatives and their antihypertensive activities. Eur. J. Med. Chem. 2004 39 12 1089 1095 10.1016/j.ejmech.2004.09.005 15571871
    [Google Scholar]
  63. Demirayak S. Karaburun A.C. Kayagil I. Erol K. Sirmagul B. Some pyridazinone and phthalazinone derivatives and their vasodilator activities. Arch. Pharm. Res. 2004 27 1 13 18 10.1007/BF02980038 14969331
    [Google Scholar]
  64. Mishra R. Siddiqui A.A. Husain A. Rashid M. Goda C. Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives. J. Enzyme Inhib. Med. Chem. 2013 28 3 552 559 10.3109/14756366.2012.656623 22380781
    [Google Scholar]
  65. Flefel E. Tantawy W. El-Sofany W. El-Shahat M. El-Sayed A. Abd-Elshafy D. Synthesis of some new pyridazine derivatives for anti-HAV evaluation. Molecules 2017 22 1 148 10.3390/molecules22010148 28106751
    [Google Scholar]
  66. Livermore D.G.H. Bethell R.C. Cammack N. Hancock A.P. Hann M.M. Green D.V.S. Lamont R.B. Noble S.A. Orr D.C. Payne J.J. Synthesis and anti-HIV-1 activity of a series of imidazo[1,5-b]pyridazines. J. Med. Chem. 1993 36 24 3784 3794 10.1021/jm00076a005 7504733
    [Google Scholar]
  67. Okushima H. Narimatsu A. Kobayashi M. Furuya R. Tsuda K. Kitada Y. A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives. J. Med. Chem. 1987 30 7 1157 1161 10.1021/jm00390a007 3599022
    [Google Scholar]
  68. Bristol J.A. Sircar I. Moos W.H. Evans D.B. Weishaar R.E. Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: Novel positive inotropic agents for the treatment of congestive heart failure. J. Med. Chem. 1984 27 9 1099 1101 10.1021/jm00375a001 6471063
    [Google Scholar]
  69. Mertens A. Friebe W.G. Mueller-Beckmann B. Kampe W. Kling L. Von der Saal W. Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities. J. Med. Chem. 1990 33 10 2870 2875 10.1021/jm00172a031 2213839
    [Google Scholar]
  70. Rüegg J.C. Pfitzer G. Eubler D. Zeugner C. Effect on contractility of skinned fibres from mammalian heart and smooth muscle by a new benzimidazole derivative, 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methy l-3(2H)- pyridazinone. Arzneimittelforschung 1984 34 12 1736 1738 6543308
    [Google Scholar]
  71. Sircar I. Duell B.L. Bobowski G. Bristol J.A. Evans D.B. Cardiotonic agents. 2. Synthesis and structure-activity relationships of 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: A new class of positive inotropic agents. J. Med. Chem. 1985 28 10 1405 1413 10.1021/jm00148a006 2864447
    [Google Scholar]
  72. Wang L. Zhou H. Yang B. Chen Z. Yang H. Synthesis and anti-congestive heart failure activity of novel levosimendan analogues. Med. Chem. Res. 2011 20 3 287 292 10.1007/s00044‑010‑9319‑0
    [Google Scholar]
  73. Abouzid K. Abdel Hakeem 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]
  74. Mohan C.G. Kumar A. Mishra P.C. Electric field mapping and structure-activity relationships for some dihydropyridazinone cardiotonics. J. Mol. Struct. THEOCHEM 1995 332 1-2 171 176 10.1016/0166‑1280(94)03904‑Y
    [Google Scholar]
  75. Lee A.R. Huang W.H. Lin T.L. Shih K.M. Lee H.F. Lin C.I. Synthesis of 1,3‐dihydro‐3,3‐dimethyl‐2 H ‐indol‐2‐one derivatives as possible nonsteroidal cardiotonics. J. Heterocycl. Chem. 1995 32 1 1 11 10.1002/jhet.5570320101
    [Google Scholar]
  76. Combs D.W. Synthesis and cardiotonic activity of 2,9-dihydro-6-(5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-yl)pyrazolo[4,3-b][1,4]benzoxazine. Bioorg. Med. Chem. Lett. 1993 3 8 1663 1666 10.1016/S0960‑894X(00)80038‑4
    [Google Scholar]
  77. Yuzhakov S.D. Mastafanova L.I. Mashkovskii M.D. Yakhontov L.N. Relationship between the structure and effects of cardiotonics with nonglycoside and noncatecholamine structure. Pharm. Chem. J. 1992 26 3 191 209 10.1007/BF00772931
    [Google Scholar]
  78. Huang Q. Qian X. Song G. Cao S. The toxic and anti‐feedant activity of 2 H ‐pyridazin‐3‐one‐substituted 1,3,4‐oxadiazoles against the armyworm Pseudaletia separata (Walker) and other insects and mites. Pest Manag. Sci. 2003 59 8 933 939 10.1002/ps.704 12916775
    [Google Scholar]
  79. Dang M. Liu M. Huang L. Ou X. Long C. Liu X. Ren Y. Zhang P. Huang M. Liu A. Design, synthesis, and bioactivities of novel pyridazinone derivatives containing 2‐phenylthiazole or oxazole skeletons. J. Heterocycl. Chem. 2020 57 11 4088 4098 10.1002/jhet.4118
    [Google Scholar]
  80. Cao S. Qian X. Song G. Chai B. Jiang Z. Synthesis and antifeedant activity of new oxadiazolyl 3(2H)-pyridazinones. J. Agric. Food Chem. 2003 51 1 152 155 10.1021/jf0208029 12502400
    [Google Scholar]
  81. Cao S. Wei N. Zhao C. Li L. Huang Q. Qian X. Syntheses, antifeedant activity, and QSAR analysis of new oxa(thia)diazolyl 3(2H)-pyridazinones. J. Agric. Food Chem. 2005 53 8 3120 3125 10.1021/jf047985e 15826068
    [Google Scholar]
  82. Rinderspacher A. Chapter 5.2 six-membered ring systems: Diazines and benzo derivatives. Progress in Heterocyclic Chemistry Gribble G.W. Joule J.A. Elsevier Amsterdam, Netherlands 2013 25 357 390
    [Google Scholar]
  83. Lahue B.R. Woo G.H.C. Snyder J.K. Chapter 6.2 six-membered ring systems: Diazines and benzo derivatives. Progress in Heterocyclic Chemistry Gribble G.W. Gilchrist T.L. Elsevier Amsterdam, Netherlands 2001 13 261 295
    [Google Scholar]
  84. Lahue B.R. Snyder J.K. Chapter 6.2 six-membered ring systems: Diazines and benzo derivatives. Progress in Heterocyclic Chemistry Gribble G.W. Gilchrist T.L. Elsevier Amsterdam, Netherlands 2000 12 263 293
    [Google Scholar]
  85. Manlove A. Groziak M.P. Chapter 6.2 six-membered ring systems: Diazines and benzo derivatives. Progress in Heterocyclic Chemistry Gribble G.W. Joule J.A. Elsevier Amsterdam, Netherlands 2009 20 333 363
    [Google Scholar]
  86. Kang S. Moon H.K. Yoon Y.J. Yoon H.J. Recent progress in the chemistry of pyridazinones for functional group transformations. J. Org. Chem. 2018 83 1 1 11 10.1021/acs.joc.7b02481 29207874
    [Google Scholar]
  87. Han Y.T. Jung J-W. Kim N-J. Recent advances in the synthesis of biologically active cinnoline, phthalazine and quinoxaline derivatives. Curr. Org. Chem. 2017 21 14 1265 1291 10.2174/1385272821666170221150901
    [Google Scholar]
  88. Jaballah M. Serya R. Abouzid K. Pyridazine based scaffolds as privileged structures in anti-cancer therapy. Drug Res. 2017 67 3 138 148 10.1055/s‑0042‑119992 28073115
    [Google Scholar]
  89. Miller M.M. DelMonte A.J. Chapter 6.2 six-membered ring systems: Diazines and benzo derivatives. Progress in Heterocyclic Chemistry Gribble G.W. Joule J.A. Elsevier Amsterdam, Netherlands 2011 23 371 402
    [Google Scholar]
  90. Katritzky A.R. Rees C.W. 1.01 - Introduction. Comprehensive Heterocyclic Chemistry. Katritzky A.R. Rees C.W. Oxford Pergamon 1984 1 6
    [Google Scholar]
  91. Coates W.J. 6.01 - Pyridazines and their benzo derivatives. Comprehensive Heterocyclic Chemistry II. Katritzky A.R. Rees C.W. Scriven E.F.V. Oxford Pergamon 1996 1 91 10.1016/B978‑008096518‑5.00117‑9
    [Google Scholar]
  92. Maes B.U.W. Lemière G.L.F. 8.01 - Pyridazines and their benzo derivatives. Comprehensive Heterocyclic Chemistry III. Katritzky A.R. Ramsden C.A. Scriven E.F.V. Taylor R.J.K. Oxford Elsevier 2008 1 116 10.1016/B978‑008044992‑0.00701‑X
    [Google Scholar]
  93. Sergeev P.G. Nenajdenko V.G. Recent advances in the chemistry of pyridazine — an important representative of six-membered nitrogen heterocycles. Russ. Chem. Rev. 2020 89 4 393 429 10.1070/RCR4922
    [Google Scholar]
  94. Coates W.J. Mckillop A. One-pot preparation of 6-substituted 3(2 H)-Pyridazinones from ketones. Synthesis 1993 1993 3 334 342 10.1055/s‑1993‑25861
    [Google Scholar]
  95. Buysse A.M. Yap M.C.H. Hunter R. Babcock J. Huang X. Synthesis and biological activity of pyridazine amides, hydrazones and hydrazides. Pest Manag. Sci. 2017 73 4 782 795 10.1002/ps.4465 27766752
    [Google Scholar]
  96. 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]
  97. Bell R.P. Earls D.W. Timimi B.A. Inter- and intra-molecular catalysis in the iodination of o-hydroxyacetophenone. J. Chem. Soc., Perkin Trans. 2 1974 7 811 817 10.1039/p29740000811
    [Google Scholar]
  98. Zare L. Mahmoodi N. Yahyazadeh A. Mamaghani M. Tabatabaeian K. An efficient one‐pot synthesis of pyridazinones and phthalazinones using HY‐zeolite. J. Heterocycl. Chem. 2011 48 4 864 867 10.1002/jhet.649
    [Google Scholar]
  99. Botero Cid H.M. Tränkle C. Baumann K. Pick R. Mies-Klomfass E. Kostenis E. Mohr K. Holzgrabe U. Structure-activity relationships in a series of bisquaternary bisphthalimidine derivatives modulating the muscarinic M(2)-receptor allosterically. J. Med. Chem. 2000 43 11 2155 2164 10.1021/jm991136e 10841794
    [Google Scholar]
  100. Jolivet S. Texier-Boullet F. Hamelin J. Jacquault P. New method for the synthesis of 3(2H)‐pyridazinones and their alkene precursors: Solvent‐free reactions under microwave irradiation. Heteroatom Chem. 1995 6 5 469 474 10.1002/hc.520060512
    [Google Scholar]
  101. Patil A.M. Lagad P.M. Soge B. Meshram R. Lokhande M.N. Lokhande P.D. Ammonium chloride mediated synthesis of 2-aryl-phthalazinone from O-formyl benzoic acid and in silico applications. ARKIVOC 2023 2023 7 202311972 10.24820/ark.5550190.p011.972
    [Google Scholar]
  102. Ellis J.E. Davis E.M. Brower P.L. A novel and practical method for hydrocyanation of chalcones. Org. Process Res. Dev. 1997 1 3 250 252 10.1021/op960048q
    [Google Scholar]
  103. Sotelo E. Mocelo R. Suárez M. Loupy A. Synthesis of polyfunctional pyridazine derivatives using a solvent-free microwave assisted method. Synth. Commun. 1997 27 14 2419 2423 10.1080/00397919708004105
    [Google Scholar]
  104. Hovakimyan S.A. Babakhanyan A.V. Voskanyan V.S. Karapetian V.E. Panosyan G.A. Kocharian S.T. Synthesis of pyridazinone derivatives. Chem. Heterocycl. Compd. 2004 40 8 1047 1051 10.1023/B:COHC.0000046696.37815.62
    [Google Scholar]
  105. Kodama T. Sasaki I. Sugimura H. Synthesis of pyridazine derivatives via aza-diels-alder reactions of 1,2,3-triazine derivatives and 1-propynylamines. J. Org. Chem. 2021 86 13 8926 8932 10.1021/acs.joc.1c00851 34132555
    [Google Scholar]
  106. Attanasi O.A. Favi G. Filippone P. Perrulli F.R. Santeusanio S. A novel and convenient protocol for synthesis of pyridazines. Org. Lett. 2009 11 2 309 312 10.1021/ol802432z 19072699
    [Google Scholar]
  107. Chantegrel B. Deshayes C. Pujol B. Wei Z.J. Synthesis of isoxazolo[4,5‐d]pyridazin‐4(5 H)‐ones and 4‐acyl‐5‐hydroxy‐3(2 H)‐pyridazinones. J. Heterocycl. Chem. 1990 27 4 927 934 10.1002/jhet.5570270420
    [Google Scholar]
  108. Hote B.S. Sawant A.S. Sawant S.S. SiO 2 -BiCl 3 as heterogeneous catalyzed synthesis of 6-Methyl-2-aryl-4,5-dihydropyridazin-3(2 H)-one derivatives. Polycycl. Aromat. Compd. 2020 40 5 1501 1509 10.1080/10406638.2018.1557708
    [Google Scholar]
  109. Karadeniz E. Zora M. Synthesis of 1-Azaspiro[4.5]deca-1,3-dienes from N-Propargylic β-Enaminones in Basic Medium. Synthesis 2019 51 10 2157 2170 10.1055/s‑0037‑1611723
    [Google Scholar]
  110. Karadeniz E. Zora M. One-pot synthesis of spiro-2h-pyrroles from n-propargylic β-enaminones. Synlett 2019 30 10 1231 1236 10.1055/s‑0037‑1611816
    [Google Scholar]
  111. Dundar B.A. Zora M. A facile synthesis of a novel family of heterotricyclic hybrids: Spiro-pyrrolopyridazines. Synth. Commun. 2022 52 3 356 367 10.1080/00397911.2021.2024575
    [Google Scholar]
  112. Chinchilla R. Nájera C. The Sonogashira reaction: A booming methodology in synthetic organic chemistry. Chem. Rev. 2007 107 3 874 922 10.1021/cr050992x 17305399
    [Google Scholar]
  113. Humphries P.S. Oliver R.M. Facile synthesis of 4,5-disubstituted-3(2H)-pyridazinones. Tetrahedron Lett. 2009 50 22 2682 2684 10.1016/j.tetlet.2009.03.144
    [Google Scholar]
  114. Ma C. Liu S.J. Xin L. Falck J.R. Shin D.S. Novel formation of 1,3-oxazepine heterocycles via palladium-catalyzed intramolecular coupling reaction. Tetrahedron 2006 62 38 9002 9009 10.1016/j.tet.2006.07.009
    [Google Scholar]
  115. Bel Abed H. Mammoliti O. Bande O. Van Lommen G. Herdewijn P. Strategy for the synthesis of pyridazine heterocycles and their derivatives. J. Org. Chem. 2013 78 16 7845 7858 10.1021/jo400989q 23947534
    [Google Scholar]
  116. Hu Z. Wang C. Han W. Rossi K.A. Bozarth J.M. Wu Y. Sheriff S. Myers J.E. Luettgen J.M. Seiffert D.A. Wexler R.R. Quan M.L. Pyridazine and pyridazinone derivatives as potent and selective factor XIa inhibitors. Bioorg. Med. Chem. Lett. 2018 28 6 987 992 10.1016/j.bmcl.2018.02.049 29501396
    [Google Scholar]
  117. Malinka W. Redzicka A. Jastrzębska - Więsek M. Filipek B. Dybała M. Karczmarzyk Z. Urbańczyk-Lipkowska Z. Kalicki P. Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents. Eur. J. Med. Chem. 2011 46 10 4992 4999 10.1016/j.ejmech.2011.08.006 21864951
    [Google Scholar]
  118. Hoogenboom R. Moore B.C. Schubert U.S. Microwave-assisted synthesis of 3,6-di(pyridin-2-yl)pyridazines: Unexpected ketone and aldehyde cycloadditions. J. Org. Chem. 2006 71 13 4903 4909 10.1021/jo060632p 16776520
    [Google Scholar]
  119. Nabid M.R. Rezaei S.J.T. Ghahremanzadeh R. Bazgir A. Ultrasound-assisted one-pot, three-component synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones. Ultrason. Sonochem. 2010 17 1 159 161 10.1016/j.ultsonch.2009.06.012 19589715
    [Google Scholar]
  120. Kümmerle A.E. Vieira M.M. Schmitt M. Miranda A.L.P. Fraga C.A.M. Bourguignon J.J. Barreiro E.J. Design, synthesis and analgesic properties of novel conformationally-restricted N-acylhydrazones (NAH). Bioorg. Med. Chem. Lett. 2009 19 17 4963 4966 10.1016/j.bmcl.2009.07.075 19646868
    [Google Scholar]
  121. Breukelman S.P. Meakins G.D. Roe A.M. Preparation and some reactions of 4- and 5-aryl-4,5-dihydropyridazin-3(2H)-ones. J. Chem. Soc., Perkin Trans. 1 1985 0 1627 1635 10.1039/p19850001627
    [Google Scholar]
  122. Kumagai M. Studies on Pyridazine Derivatives. IV. Synthesis of pyridazinethiols. Nippon Kagaku Zassi 1960 81 10 1604 1606 10.1246/nikkashi1948.81.10_1604
    [Google Scholar]
  123. Overend W.G. Wiggins L.F. 56. The conversion of sucrose into pyridazine derivatives. Part I. 3-Sulphanilamido-6-methylpyridazine. J. Chem. Soc. 1947 0 239 244 10.1039/jr9470000239
    [Google Scholar]
  124. Csende F. Szabó Z. Partial dehydrogenation of saturated 4-phenyl-1(2 H)-phthalazinone derivatives by thionyl chloride. Synth. Commun. 1993 23 21 2957 2964 10.1080/00397919308011137
    [Google Scholar]
  125. Csende F. Szabó Z. Bernáth G. Stájer G. Copper(II) chloride as an efficient reagent for the dehydrogenation of pyridazinone derivatives. Synthesis 1995 1995 10 1240 1242 10.1055/s‑1995‑4079
    [Google Scholar]
/content/journals/mroc/10.2174/0118756298421529251030163718
Loading
/content/journals/mroc/10.2174/0118756298421529251030163718
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test