Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-b]Quinazolin-9(1H)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction
2025
Davron Turgunov | Lifei Nie | Azizbek Nasrullaev | Zarifa Murtazaeva | Bianlin Wang | Dilafruz Kholmurodova | Rustamkhon Kuryazov | Jiangyu Zhao | Khurshed Bozorov | Haji Akber Aisa
An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer&rsquo:s disease. The conditions for the Suzuki&ndash:Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman&rsquo:s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC50 value of 6.084 ±: 0.26 &mu:M. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer&rsquo:s disease.
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