Alagoz, Mehmet Abdullah published the artcileDevelopment of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors, HPLC of Formula: 17259-32-4, the main research area is pyridazinone derivative development MAOB inhibitor; PAMPA; docking; kinetics; monoamine oxidase-B; pyridazinones; reversibility.
Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 μM, followed by TR2 (IC50 = 0.27 μM). TR2 and TR16 selectivity index (SI) values for MAO-B vs. MAO-A were 84.96 and higher than 235.29, resp. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with Ki values of 0.230 ± 0.004 and 0.149 ± 0.016 μM, resp. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.
Molecules published new progress about Bioavailability. 17259-32-4 belongs to class pyridazine, name is 4-(6-Chloropyridazin-3-yl)morpholine, and the molecular formula is C8H10ClN3O, HPLC of Formula: 17259-32-4.
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem