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.

Background: Among Nitrogen-containing heterocyclic compounds, pyridazine derivatives serve as a necessary scaffold as they possess various pharmacological activities. Thus, in recent times, the design of novel synthetic schemes and the selection of a new target for the action of pyridazine derivatives have attracted the attention of researchers. Objective: This study has focused on synthesizing and evaluating the muscle relaxant activity of pyridazine analogs by in-silico screening and rotarod test. Methods: In the present work, pyridazine derivatives were synthesized from substituted pyridine and maleic anhydride yielding intermediates (1a-5a) which on reaction with hydrazine yielded final pyridazine derivatives(1b-5b). They were then screened for muscle relaxant action by an in-silico docking study against muscarinic acetylcholine receptors with protein data bank ID: 5CXV with the use of Autodock 4.2 and Biovia discovery studio tools. Compounds were further tested for muscle relaxant activity by the rotarod test Results: Synthesis of the designed compounds was carried out successfully. Obtained result showed that the final compounds (1b-5b) showed 1-3 interactions with acetylcholine muscarinic receptor with -7.2 to -7.9 Kcal/mole affinities. The findings were compared to the typical drug diazepam, which has one interaction with the target and binding energy of -7.7 Kcal/mole. Moreover, the result of the rotarod test showed that substitution by electron-withdrawing groups causes more muscle relaxant activity when compared with the electron releasing groups Conclusion: The results of the experimental study showed that pyridazine derivatives could serve as a promising template for the further design and development of muscle relaxant agents.