Pflegr, Vaclav; Stepankova, Sarka; Svrckova, Katarina; Svarcova, Marketa; Vinsova, Jarmila; Kratky, Martin published the artcile< 5-Aryl-1,3,4-oxadiazol-2-amines Decorated with Long Alkyl and Their Analogues: Synthesis, Acetyl- and Butyrylcholinesterase Inhibition and Docking Study>, Application In Synthesis of 93-60-7, the main research area is aryloyl dodecyl oxadiazol amine preparation cholinesterase inhibition docking SAR; dodecyl aryloyl thiadiazol amine preparation acetyl butyrylcholinesterase inhibition docking; hydrazine carboxamide cyclization; 1,3,4-oxadiazole; 1,3,4-thiadiazole; acetylcholinesterase; butyrylcholinesterase; enzyme inhibition; molecular docking.
The compounds 5-aryl-1,3,4-oxadiazoles/thiadiazols decorated with dodecyl linked via nitrogen, sulfur or directly to this heterocycle I [R = Ph, 4-MeC6H4, 4-tBuC6H4, etc.,; X = O, S; Y = NH, S] was designed as potential inhibitors of AChE and BChE. Oxadiazoles/thiadiazols derivatives I were prepared from hydrazides by reaction with dodecyl isocyanate to form hydrazine-1-carboxamides II (yields 67-98%) followed by cyclization using p-toluenesulfonyl chloride and triethylamine in 41-100% yields. The derivatives I were screened for inhibition of AChE and BChE using Ellman’s spectrophotometric method. The compounds I showed a moderate dual inhibition with IC50 values of 12.8-99.2 for AChE and from 53.1μM for BChE. All the heterocycles I were more efficient inhibitors of AChE. The most potent inhibitor, N-dodecyl-5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine I [R =4-pyridyl, X= S, Y = NH] was subjected to advanced reversibility and type of inhibition evaluation. Structure-activity relationships of heterocycles I were identified. Many oxadiazoles I showed lower IC50 values against AChE than established drug rivastigmine. According to mol. docking, the compounds I interact non-covalently with AChE and BChE and block entry into enzyme gorge and catalytic site, resp.
Pharmaceuticals published new progress about Amides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 93-60-7 belongs to class pyridine-derivatives, and the molecular formula is C7H7NO2, Application In Synthesis of 93-60-7.