2166-13-4Relevant articles and documents
Rhodium(III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2H)-one Scaffolds via C-H Bond Activation
Du, Xuxin,Hou, Hongcen,Zhao, Yongli,Sheng, Shouri,Chen, Junmin
, p. 1100 - 1107 (2020)
Selective C–H bond alkynylation toward modular access to material and pharmaceutical molecules is of great desire in modern organic synthesis. Disclosed herein is rhodium(III)-catalyzed selective C–H bond mono-/bialkynylation of 4-aryl phthalazin-1(2H)-one was developed. The silver salt AgSbF6 are demonstrated to play a vital role in promoting the bialkynylation reactions. The present alkynylation strategy is simple, efficient, and features high functional group tolerance and broad substrate scope under an air atmosphere. Additionally, 6-aryl pyridazin-3(2H)-one scaffold is amenable to the selective monoalkynylation and sequential bialkynylation, respectively.
A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies
?z?elik, Azime Berna,?zdemir, Zeynep,Sari, Suat,Utku, Semra,Uysal, Mehtap
, p. 1253 - 1263 (2019/11/03)
Background: The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of cholinesterases is an effective method to curb Alzheimer's disease. 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 molecular docking approach. Method: 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. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schr?dinger, LLC, New York, NY, 2019). Results: The title compounds showed moderate inhibition at 100 μg/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, respectively. Conclusion: 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 favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE.
Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities
Tiryaki, Didem,Sukuroglu, Murat,Dogruer, Deniz S.,Akkol, Esra,Ozgen, Selda,Sahin, M. Fethi
, p. 2553 - 2560 (2013/07/26)
In this study, 12 new 3(2H)-pyridazinone derivatives carrying 4-substituted phenylpiperazinylethyl moiety on lactam nitrogen were synthesized and their chemical structures were confirmed by 1H-NMR, mass, and elemental analysis. Analgesic and anti-inflammatory activities of the synthesized compounds were evaluated in mice. Among the synthesized compounds, compound 9c showed the best analgesic and anti-inflammatory activities without causing any gastric effect in stomachs of tested animals. In addition, the synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains.
