A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies was written by Ozcelik, Azime Berna;Ozdemir, Zeynep;Sari, Suat;Utku, Semra;Uysal, Mehtap. And the article was included in Pharmacological Reports in 2019.Reference of 2166-13-4 This article mentions the following:
AChE and BChE are known to be serine hydrolase enzymes responsible for the hydrolysis of ACh. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer’s Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using mol. docking approach. We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman’s method. Mol. docking studies were done using Glide and the results were evaluated on Maestro. The title compounds showed moderate inhibition at 100μg/mL against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, resp. This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favorable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Reference of 2166-13-4).
6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Reference of 2166-13-4
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem