An Efficient Synthesis of bi‐Aryl Pyrimidine Heterocycles: Potential New Drug Candidates to Treat Alzheimer's Disease

Abstract

A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC = 0.04 ± 0.0001 μM for AChE and IC = 0.85 ± 0.0001 μM for BChE), the IC values of the synthesized compounds ranged from 3.73 ± 0.61 μM to 57.36 ± 0.22 μM for AChE and 4.81 ± 0.16 μM to 111.61 ± 0.53 μM for BChE. Among these tested compounds, 6j having a -CH group was found to be the most potent one against both enzymes (AChE, IC = 3.73 ± 0.61 μM; BChE, IC = 4.81 ± 0.16 μM). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.

Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review

“…Additionally, the docked complex of BChE with 6j (BChE-6j) showed that the hydrophobic patch residue Tyr128 and the catalytic triad residue Ser198 were involved in intramolecular hydrogen bonding ( Fig. 25) [149].…”

Microwave Assisted Reactions of Azaheterocycles Formedicinal Chemistry Applications

“…Under MW irradiation, the reaction time is reduced about five folds and the yields were slightly higher. Rehman et al [65] synthesized new pyrimidines (83a-m) that were decorated with pyridine and sulfonamide moieties of potential interest in Alzheimer's disease. The syntheses were carried out under conventional TH and MW irradiation.…”

“…By comparison with reaction under classical TH, under MW irradiation the yields were higher (with about 20-25%) and the reaction time substantially decreased, from about 800 to 15 min. Rehman et al [65] synthesized new pyrimidines (83a-m) that were decorated with pyridine and sulfonamide moieties of potential interest in Alzheimer's disease. The syntheses were carried out under conventional TH and MW irradiation.…”

Organocatalyzed Solvent Free and Efficient Synthesis of 2,4,5‐Trisubstituted Imidazoles as Potential Acetylcholinesterase Inhibitors for Alzheimer's Disease

“…The increasing mortality rate, complexities in disease and the limited option of drugs for the curing of AD, demand new and more effective pharmacological products. Keeping these factors in view researchers is aiming to develop new potential drugs …”