Pyridazinones containing the (4-methoxyphenyl)piperazine moiety as AChE/BChE inhibitors: design, synthesis, in silico and biological evaluation was written by Merde, Irem B.;Onel, Gulce T.;Turkmenoglu, Burcin;Gursoy, Sule;Dilek, Esra. And the article was included in Medicinal Chemistry Research in 2022.COA of Formula: C4H2Cl2N2 This article mentions the following:
Alzheimer disease is a progressive and fatal neurodegenerative disease affecting the elderly population accompanied by a decrease in cholinergic transmission, impairing cognitive functions. Acetylcholine deficiency is important in the development of disease symptoms. Inhibition of acetylcholinesterase, an important enzyme in acetylcholine hydrolysis, is one of the important drug targets to increase acetylcholine levels. In this study, we aimed to develop acetylcholinesterase inhibitor compounds For this, we synthesized compounds 6(a-e) bearing 3(2H)-pyridazinone and 1,2,4-triazole ring structures. We determined the IC50, Ki and inhibition types of N-substituted-(p-methoxyphenyl)pyridazin-3(2H)-one derivatives that we synthesized and elucidated their structures. The compound with the best AChE activity was compound 6b (Ki = 3.73 ± 0.9 nM) with the p-methylphenyl group it carried and showed competitive inhibition. Kinetic study was also performed for the compounds with the highest BChE 6a (Ki = 0.95 ± 0.16 nM) inhibitory activities. Mol. docking studies have shown that the p-methylphenyl group is indeed active in the hinge region of the AChE crystal structure as a result of exptl. activity. In addition, the best free binding energy (ΔGBind), docking score and Glide score values were determined by examining the interactions with AChE crystal structure for compound 6b and with BChE crystal structure for 6a in silico approaches. Graphical abstract In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0COA of Formula: C4H2Cl2N2).
3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.COA of Formula: C4H2Cl2N2
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem