Synthesis of new heterocyclic 3-piperidinyl-1,3,4-oxadiazole derivatives as potential drug candidate for the treatment of Alzheimer’s disease

Abstract

Abstract A series of new N-substituted derivatives of 3-[(5-{1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-yl)sulfanyl]propanamide (7a–q) was synthesized to evaluate new drug candidates for Alzheimer’s disease. 4-Chlorobenzenesulfonyl chloride (a) and ethyl piperidin-3-carboxylate (b) were converted into 5-{1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-thiol (3) through a series of three steps. A series of electrophiles, N-alkyl/aralkyl/aryl-3-bromopropanamide (6a–q), was synthesized by gearing up 3-bromopropionyl chloride (5) with different alkyl/aralkyl/aryl amines (4a–q). Target compounds were synthesized by reacting compound 3 with different electrophiles, 6a–q, under basic conditions in an aprotic polar solvent. The synthesized compounds were subjected to spectral analysis, EI-MS, IR, 1H-NMR and 13C-NMR, for structural elucidation. The compounds were screened for enzyme inhibition activity against acetyl cholinesterase (AChE) enzyme. The validity of synthesized compounds as new drug candidates was also evaluated through haemolytic activity.