Aamir Malik, Rakhi Mishra, Rupa Mazumder, Avijit Mazumder, Prem Shankar Mishra
Aamir Malik1, Rakhi Mishra1*, Rupa Mazumder1, Avijit Mazumder1, Prem Shankar Mishra2
1Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida-201306, Uttar Pradesh, India.
2Galgotias University, Greater Noida-201306, Uttar Pradesh, India.
Volume - 14,
Issue - 6,
Year - 2021
Pyridazine and its derivative are very important compounds in nitrogen containing heterocyclic compounds due to their various reported pharmacological activities such as antibacterial, muscle relaxant, anti-depressant, antidiabetic, anti-hypertensive, analgesic, anti-tumor, antiviral, nephrotropic, antiinflammatory, anti-viral, anticancer, anti-aggregative, anti-epileptic. It also serves as building block in structure of many chemical constituent of natural compounds phytopharmaceuticals such as cinnolines, phthalazines and also attracting the interest of researchers and medicinal chemist due to its privilege structure which can bear substitution/functionalization easily. Different substituted pyridazine compounds have been synthesized by researchers using different reagents and diverse synthetic route. However most of the investigations available in literature are directed to its large number of biological activities with very less discussion on its various synthetic schemes yielding different type of its derivatives. With the purpose of focusing more on this lack of recent literature this review focuses on different derivative synthesis by using different reaction schemes. Now-a-days pyridazine is serving as ligand in many known chemical reactions and scaffold for drug discovery and development. The aim of this review paper is to encourage more studies on synthesis of pyridazine derivatives which in future will play a vital role for drug discovery.
Cite this article:
Aamir Malik, Rakhi Mishra, Rupa Mazumder, Avijit Mazumder, Prem Shankar Mishra. A comprehensive study on synthesis and biological activities of Pyridazine Derivatives. Research Journal of Pharmacy and Technology. 2021; 14(6):3423-9. doi: 10.52711/0974-360X.2021.00595
Aamir Malik, Rakhi Mishra, Rupa Mazumder, Avijit Mazumder, Prem Shankar Mishra. A comprehensive study on synthesis and biological activities of Pyridazine Derivatives. Research Journal of Pharmacy and Technology. 2021; 14(6):3423-9. doi: 10.52711/0974-360X.2021.00595 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-6-85
1. Al-Mulla A. A Review: Biological Importance of Heterocyclic Compounds. Der Pharma Chemica. 2017; 9(13): 141-147.
2. Kumar Pooja, Umakant, Sharma Gyanendra. Synthesis and Antibacterial activity of some newer Benzimidazole derivatives. Research J. Pharm. and Tech 2020; 13(6)):2597-2600
3. Neama, R, Dr. Aljamali NM, Dr. Jari M. Synthesis, Identification of Heterocyclic Compounds and Study of Biological Activity. Asian Journal of Research in Chemistry. 2014; 7(7): 664-676.
4. Sahoo Subhas, Sindhu K. N, Sreeveena K.. The Significance of 1, 2, 4 Triazoles in Agriculture Science: A Review. Research J. Pharm. and Tech. 2019.
5. Arora P, Arora V, Lamba H.S, Wadhwa D. Importance of Heterocyclic Chemistry: AReview. International Journal of Pharmaceutical Sciences and Research. 2012; 3(9): 2947-2955.
6. AlamM, Zaman M.S, Alam M.M, Husain A. Studies on 3,5-Disubstituted-phenyl-3,3a,4,7-tetrahydro-2H-pyrazolo[3,4-c]pyridazine derivatives. Journal of Pharmacy Research. 2014; 8(11): 1586-1591.
7. Kang S, Moon H.K, Yoon Y.J, Yoon H.J. Recent Progress in the Chemistry of Pyridazinones for Functional Group Transformations. The Journal of Organic Chemistry.2018; 83: 1−11.
8. Elagamey A.G, Sattar S.A, El-Taweel F, Said S. An Efficient Synthesis and Antibacterial Activity of Pyrido[2,3-d]Pyrimidine, Chromeno[3,4-c]Pyridine, Pyridine, Pyrimido[2,3-c]Pyridazine, Enediamines, and Pyridazine Derivatives. Journal of Heterocyclic Chemistry. 2015; 53(6): 1801-1806.
9. Devika N, Ruso J.S, Mariyappan M, Sivakumar N. Tandem Synthesis And Antibacterial Studies Of Novel 3-Substituted Tetrahydrobenzo [4,5] Thieno[1,2,4] Triazolo [4,3-B] Pyridazine And 2- (5-(Substituted) -4h-1,2,4-Triazole-3-Yl) -Tetrahydrobenzo [B] Thiophene-3-Carbonitirile Derivatives. International Journal Of Scientific and Technology Research. 2019; 8(8): 1808-1817.
10. Butnariu R.M, Mangalagiu I.I. New pyridazine derivatives: Synthesis, chemistry and biological activity. Bioorganic and Medicinal Chemistry. 2009; 17: 2823–2829.
11. Popovici L, Amarandi R.M, Mangalagiu I.I, Mangalagiu V, Danac R. Synthesis, molecular modelling and anticancer evaluation of new pyrrolo [1,2-b] pyridazine and pyrrolo [2,1-a]phthalazine derivatives.Journal of Enzyme Inhibition and Medicinal Chemistry. 2019; 34(1): 230–243.
12. Islam M, Siddiqui A.A, Rajesh R, Synthesis, antitubercular, antifungal and antibacterial activities of 6-substituted phenyl-2-(3í-substituted phenyl pyridazin-6í-yl)-2,3,4,5-tetrahydropyridazin-3-one.Acta Poloniae Pharmaceutica. 2008; 65(3): 353-362.
13. Bindu B, Vijayalakshmi S, Manikandan A. Synthesis and discovery of triazolo-pyridazine-6-yl-substituted piperazines as effective anti-diabetic drugs; evaluated over dipeptidyl peptidase-4 inhibition mechanism and insulinotropic activities. European Journal of Medicinal Chemistry.2020; 187: 1-8.
14. Allam H.A, Kamel A.A, El-Daly M, George R.F. Synthesis and vasodilator activity of some pyridazin-3(2H)-one based compounds. Future Medicinal Chemistry. 2020; 12(1): 37-50.
15. Mishra R, Siddiqui A.A, Husain A, Rashid M, Prakash A, Tailang M, Kumar M, Srivastava N. Synthesis, characterization and antihypertensive activity of some new substituted pyridazine derivatives. Journal of the Chilean Chemical Society. 2011; 56(4): 856-859.
16. Guan L.P, Sui X, Deng X.Q, Quan Y.C, Quan Z.S. Synthesis and anticonvulsant activity of a new 6-alkoxy-[1,2,4]triazolo[4,3-b]pyridazine. European Journal of Medicinal Chemistry. 2010; 45: 1746–1752.
17. 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. Archives of Pharmacal Research. 2012; 35(12): 2077-2092.
18. KoneEnk V. Synthesis and Insecticidal Properties of Some 2-Substituted-3-oxo-4-halo-5(2H)-pyridazinyl Phosphorus Esters. Pesticide Science. 1973; 4: 775-783.
19. Abubshait S.A. An Efficient Synthesis and Reactions of Novel Indolylpyridazinone Derivatives with Expected Biological Activity. Molecules. 2007; 12: 25-42.
20. Dilesh Indorkar, N. Gautam, O.P. Chourasia, S.N. Limaye. Synthesis and Characterization of Cinnoline (Benzopyridazine) and Cinnoline based Pyrazoline Derivatives and Biological Activity. Asian J. Research Chem. 6(9): September 2013; Page 832-838.
21. Dilesh Indorkar, N. Gautam, O.P. Chourasia, S.N. Limaye. Synthesis and Characterization of Cinnoline (Benzopyridazine) and Cinnoline based Pyrazoline Derivatives and Biological Activity. Asian J. Research Chem. 6(9): September 2013; Page 832-838.
22. Wang H, Xiao J, Gao D, Zhang X, Yan H, Gong Z, Sun T, Li S. Pharmacophore-based design, synthesis, and biological evaluation of novel chloro-pyridazine piperazines as human rhinovirus (HRV-3) inhibitors. Bioorganic & Medicinal Chemistry Letters. 2011; 21: 1057–1059.
23. Tucaliuc R.B, Risca I.M, Drochioiu G, Mangalagiu I. Biological effect of some new pyridazine derivatives on wheat in germination experiments.Romanian Biotechnological Letters. 2008; 13(4): 38373842.
24. V. Ravichandiran ,Sankaradoss Nirmala. A systematic Review on Antidiabetic medicinal Plants. Research J. Pharmacognosy and Phytochemistry 2013; 5(3): 155-168.
25. Punasiya R, Joshi A, Yadav S, Patidar K, Kapse K. Antimicrobial Activity of the Leaves Extract of Punica granatum Linn. Research J. Pharmacognosy and Phytochemistry 2010; 2(1): 21-24
26. Kaumil Navnitbhai Modi, Palakben K. Parikh, Hiren M. Marvaniya, Dhrubo Jyoti Sen. Structure Activity Relationship Studies of Substituted Mannich Bases of Pyrazolo [1, 2-A][1,2,4,6]-Tetrazepine-3,7-Dione Ring System with Variable Electronegative Atoms (Urea/Thiourea/Guanidine) for Antimicrobial and Antifungal Activity. Asian J. Research Chem. 4(5): May, 2011; Page 838-844.
27. Javed A, Sapra S, Alam A. Synthesis, antimicrobial activity, and docking study of some N3, N6‑diphenylpyridazine‑3,6‑diamine derivatives as dihydrofolate reductase inhibitors.International Journal of Pharmaceutical Investigation. 2018; 8: 138-144.
28. Hosny M, El-Mariah F, Deeb A. Pyridazine Derivatives and Related Compounds Part 24. Synthesis and Antimicrobial Activity of Some Sulfamoylpyrazolo[3,4-c]pyridazine Derivatives. Phosphorus, Sulfur, and Silicon and the Related Elements. 2007; 182(7): 1475-1482.
29. Kandile N.G, Zaky H.T. New pyrano[2,3-c]pyridazine derivatives with antimicrobial activity synthesized using piperidine as the organocatalyst. Journal of Enzyme Inhibition and Medicinal Chemistry. 2015; 30(1): 44–51.
30. Unnissa S.H, Rajan D. Drug design, development and biological screening of pyridazine derivatives. Journal of Chemical and Pharmaceutical Research. 2016; 8(8): 999-1004.
31. Fan L, Luo Z, Li Y, Liu X, Fan J, Xue W, Tang L, Li Y. Synthesis and antifungal activity of imidazo[1,2-b]pyridazine derivatives against phytopathogenic fungi. Bioorganic & Medicinal Chemistry Letters. Lett. 2020;
32. Wu J, Song B, Chen H, Bhadury P, Hu D. Synthesis and Antifungal Activity of 5-Chloro-6-Phenylpyridazin-3(2H)-one Derivatives. Molecules. 2009; 14: 3676-3687.
33. Paidi K.R, Tatipamula V.B, Kolli M.K, Annam S.S.P, Pedakotla V.R. Synthesis of Imidazo [1,2-b] pyridazine Comprised Piperazine, Morpholine Derivatives as Potent Antimycobacterial Agents with in vivo Locomotor Activity. Anti-Infective Agents. 2017; 15(2): 131-139.
34. Asif M, Singh A. Anticonvulsant Activities of 4-benzylidene-6-(4-methyl-phenyl)-4,5-dihydropyridazin-(2H)-ones and 4-benzylidene-6-(4-chlorophenyl)-4,5-dihydropyridazin-(2H)-ones. Open Pharmaceutical Sciences Journal. 2016; 3: 203-214.
35. Sivakumar R, Anbalagan N, Gunasekaran V, Leonard J.T. Synthesis and Anticonvulsant Activity of Novel 1-Substituted-1,2-dihydropyridazine-3,6-diones.Biological and Pharmaceutical Bulletin. 2003; 26(10): 1407-1411.
36. Kota T.V.R, Gandham H, Sanasi P.D. Synthesis, characterization, and antidiabetic activity of 6-methoxyimidazo[1,2-b]pyridazine derivatives. Journal of the Chinese Chemical Society. 2019; 1-8.
37. Elmeligie S, Ahmed E.M, Abuel-Maaty S.M, Zaitone S.A.B, Mikhail D.S. Design and Synthesis of Pyridazine Containing Compounds with Promising Anticancer Activity. Chemical and Pharmaceutical Bulletin. 2017; 65: 236–247.
38. V Murugan, S Revathi, K Sumathi, Geetha KM, Kalpana Divekar. Synthesis of Some 1 - [Bis - N, N - (2 - Chloroethyl) Aminoacetyl] - 3, 5-Disubstituted -1, 2 - Pyrazolines as Possible Alkylating Anticancer Agents. Asian J. Research Chem. 3(2): April- June 2010; Page 496-499.
39. S. N. Battin, A. H. Manikshete, S. K. Sarasamkar, M. R. Asabe, D. J. Sathe. Synthesis, Spectral, Antibacterial, Antifungal and Anticancer activity Studies of Schiff bases Derived from O-Vanillin and Aminoquinolines. Asian J. Research Chem. 2017; 10(5): 660-668. doi: 10.5958/0974-4150.2017.00112.2
40. Kishore Kumar Valluri, Tejeswara Rao Allaka, I V Kasi Viswanath, Nagaraju PVVS. Design, molecular docking studies of oxaprozin linked to 4-thiazolidinone derivatives as a potent anticancer, analgesic and antiinflammatory agents. Asian J. Research Chem. 2018; 11(3):617-627. doi: 10.5958/0974-4150.2018.00111.6
41. Paidi K.R, Tatipamula V.B, Kolli M.K, Pedakotla V.R. Benzohydrazide incorporated Imidazo [1,2-b] pyridazine: Synthesis, Characterization and in vitro Anti-tubercular Activity. International Journal of Chemical Science. 2017; 15(3): 1-8.
42. Asif M. General study of pyridazine compounds against cyclooxygenase enzyme and their relation with analgesic, anti-inflammatory and anti-arthritic activities. Chronicles of Young Scientists. 2010; 1(3): 3-9.
43. Ewies E.F, El-Shehry M.F, Boulos L.S. Synthesis of Some Novel Pyridazine Derivatives of Expected Antitumor Activity. International Journal of ChemTech Research.2014-2015; 7(5): 2506-2513.
44. Asif M, Abida, Imran M. Study of Various Fused Heterocyclic Pyridazine Derivatives as Potent Anticancer Agents: A Brief Overview. Acta Scientific Pharmaceutical Sciences. 2019; 3(9): 43-49.
45. Abhishek Kumar, Prerana Shetty, Amrutha C. L, Derin Reona Vaz, Ashlin Baby. Synthesis and Antimicrobial Evaluation of Some Novel Derivatives of Coumarin Moiety. Research J. Pharm. and Tech. 2016; 9(5): 545-548. doi: 10.5958/0974-360X.2016.00103.7
46. Puttaraj C., Chetan M. Bhalgat, Sandeep K. Chitale, B. Ramesh. Synthesis and Biological Activities of Some Novel Heterocyclic Compounds Containing Thiazolidinone Derivatives. Research J. Pharm. and Tech. 4(6): June 2011; Page 972-975.
47. Asif M. The anticancer potential of various substituted pyridazines and related compounds.International Journal of Advanced Chemistry. 2014; 2(2): 148-161.
48. Flefel E.M, Tantawy W.A, El-Sofany W.I, El-Shahat M, El-Sayed A.A, Abd-Elshafy D.N. Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation. Molecules. 2017; 22(1): 1-15
49. Abed H.b, Mammoliti O, Bande O, Lommen G.V, Lommen P. Strategy for the synthesis of pyridazine heterocycles and its derivatives. The Journal of Organic Chemistry.2013; 78(16): 7845-7858.
50. T Srinivas Rao, HG Akkamma, BS Vikram. Synthesis and In Vitro Antifungal and Anthelmintic Activity Studies of Some Substituted Aryloxy-4-Thiazolidinones. Asian J. Research Chem. 3(2): April- June 2010; Page 508-512