Synthesis of novel aryl-substituted 2-aminopyridine derivatives by the cascade reaction of 1,1-enediamines with vinamidinium salts to develop novel anti-Alzheimer agents DOI Creative Commons

Sama Loori,

Hormoz Pourtaher,

Abdolmohammad Mehranpour

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 14, 2024

Abstract Alzheimer’s disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current interventions are limited underscore the need for novel inhibitors of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), enzymes implicated in pathogenesis AD. In this study, we report synthetic strategy generation 2-aminopyridine derivatives via two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (Et 3 N). The protocol introduces rapid, efficient, scalable pathway, achieving good to excellent yields while maintaining simplistic workup procedures. Seventeen were synthesized subsequently screened their inhibitory activity against AChE BChE. most potent derivative, 3m , exhibited an IC 50 value 34.81 ± 3.71 µM 20.66 1.01 BChE compared positive control donepezil 0.079 0.05 10.6 2.1 Also, detailed kinetic studies undertaken elucidate modes enzymatic inhibition compounds both promising compound was then subjected molecular docking dynamics simulations, revealing significant binding affinities favorable interaction profiles silico ADMET assessments further determined drug-like properties suggesting it as candidate pre-clinical development.

Language: Английский

Current pharmacophore based approaches for the development of new anti-Alzheimer’s agents DOI
Prachi Sharma,

Sunil Sharma,

Yogesh Yadav

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 113, P. 117926 - 117926

Published: Sept. 13, 2024

Language: Английский

Citations

3
Synthesis of novel aryl-substituted 2-aminopyridine derivatives by the cascade reaction of 1,1-enediamines with vinamidinium salts to develop novel anti-Alzheimer agents DOI Creative Commons

Sama Loori,

Hormoz Pourtaher,

Abdolmohammad Mehranpour

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 14, 2024

Abstract Alzheimer’s disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current interventions are limited underscore the need for novel inhibitors of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), enzymes implicated in pathogenesis AD. In this study, we report synthetic strategy generation 2-aminopyridine derivatives via two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (Et 3 N). The protocol introduces rapid, efficient, scalable pathway, achieving good to excellent yields while maintaining simplistic workup procedures. Seventeen were synthesized subsequently screened their inhibitory activity against AChE BChE. most potent derivative, 3m , exhibited an IC 50 value 34.81 ± 3.71 µM 20.66 1.01 BChE compared positive control donepezil 0.079 0.05 10.6 2.1 Also, detailed kinetic studies undertaken elucidate modes enzymatic inhibition compounds both promising compound was then subjected molecular docking dynamics simulations, revealing significant binding affinities favorable interaction profiles silico ADMET assessments further determined drug-like properties suggesting it as candidate pre-clinical development.

Language: Английский

Citations

2