Synthesis and pharmacological evaluation of novel N-alkyl/aryl substituted thiazolidinone arecoline analogues as muscarinic receptor 1 agonist in Alzheimer's dementia models

Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline analogues as muscarinic receptor 1 agonist in Alzheimer's dementia models. To elucidate further our SAR study on the chemistry and muscarinic receptor binding efficacy, a series of novel N-alkyl/aryl substituted thiazolidinone arecoline analogues 6(a–m) were designed and synthesized from 3-pyridine carboxaldehyde by reacting with different amines in the presence of γ-ferrite as catalyst and subjected to in vitro muscarinic receptor binding studies using male Wistar rat brain membrane homogenate and extended to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Derivative 6j having diphenylamine moiety attached to nitrogen of thiazolidinone showed significant affinity for the M1 receptor binding.

Graphical abstract A series of thiazolidinone arecolines 6(a–m) were synthesized and subjected to in vitro muscarinic receptor binding studies using male Wistar rat brain membrane homogenate and in vivo pharmacological evaluation of memory and learning.Figure optionsDownload full-size imageDownload as PowerPoint slide