Experimental and theoretical study of pyrazole N-alkylation catalyzed by basic modified molecular sieves

Matos, Inês; Pérez‐Mayoral, Elena; Soriano, Elena; Zukal, Arnošt; Martı́n-Aranda, R.M.; López-Peinado, A.J.; Fonseca, Isabel; Čejka, Jiřı́

doi:10.1016/j.cej.2009.09.040

Cited by 16 publications

(2 citation statements)

References 40 publications

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“…23 Nitrogencontaining heterocycles are abundant in nature and are also present in many natural products such as various alkaloids, vitamin derivatives, antibiotics, and hormones. 24 Approximately 60% of approved drugs are known to contain heterocyclic nitrogen in their structure. Pyrimidine and its various analogs have received great attention due to the various biological activities they possess.…”

Section: Introductionmentioning

confidence: 99%

“…Heterocyclic compounds have a very large place in medicinal chemistry, agricultural chemicals, polymer materials, and various industrial products 23 . Nitrogen‐containing heterocycles are abundant in nature and are also present in many natural products such as various alkaloids, vitamin derivatives, antibiotics, and hormones 24 . Approximately 60% of approved drugs are known to contain heterocyclic nitrogen in their structure.…”

Section: Introductionmentioning

confidence: 99%

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Pyrimidines: Molecular docking and inhibition studies on carbonic anhydrase and cholinesterases

Duran

2022

Biotech and App Biochem

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Alzheimer's disease (AD) is a neurodegenerative disorder. The disease is characterized by dementia, memory impairment, cognitive impairment, and speech impairment. Cholinesterases (ChEs; AChE, acetylcholinesterase and BChE, butyrylcholinesterase) inhibitors and their benefits of cholinergic replacement in the treatment of AD have been researched and documented by scientists in various ways to date. Recent studies prove that human carbonic anhydrases (hCAs) are also one of the important targets in the treatment of AD. Therefore, the development of new agents that can simultaneously modulate the various mechanisms or targets involved in the AD pathway may be a powerful strategy to treat AD, the current disease. Considering these data, the effects of the pyrimidines (1–7) were investigated in this study for the discovery and development of multitargeted ChEs and hCAs inhibitors associated with AD. In addition, the molecular docking analysis of the 4‐amino‐2‐choloropyrimidine (2) was performed to understand the binding interactions on the active site of the enzyme. All compounds (1–7) showed satisfactory enzyme inhibitory potency in micromolar concentrations against AChE, BChE, hCAI, and hCAII with KI values ranging from 0.099 to 0.241 μM, from 1.324 to 3.418 μM, from 0.201 to 0.884 μM, from 1.867 to 3.913 μM, respectively. Due to their ChEs and hCAs inhibition, these compounds (1–7) may be considered as leads for investigations in neurodegenerative diseases. All these results revealed that the 4‐amino‐5,6‐dichloropyrimidine (7) (KI value of 0.201 ± 0.041 μM for hCA I), the 4‐amino‐6‐hydroxypyrimidine (4) (KI value of 1.867 ± 0.296 μM for hCA II), the 4‐amino‐5,6‐dichloropyrimidine (7) (KI value of 0.099 ± 0.008 μM for AChE), and the 4‐amino‐2‐chloropyrimidine (2) (KI value of 1.324 ± 0.273 μM for BChE) from the pyrimidines in this series were the most promising derivatives, as they exhibited a good multifunctional inhibition at all experimental levels and in the in silico validation against these enzymes, for the treatment of AD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pyrimidines: Molecular docking and inhibition studies on carbonic anhydrase and cholinesterases

Duran

2022

Biotech and App Biochem

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Synthesis of N‐alkylated pyrazolo[3,4‐d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties

Aydın

Anıl

Demir

2021

Archiv der Pharmazie

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Fused pyrimidines, especially pyrazolo [3,4-d]pyrimidines, are among the most preferred building blocks for pharmacology studies, as they exhibit a broad spectrum of biological activity. In this study, new derivatives of pyrazolo [3,4-d]pyrimidine were synthesized by alkylation of the N1 nitrogen atom. We synthesized 3-iodo-1H-pyrazolo [3,4-d] pyrimidin-4-amine 2 from commercially available aminopyrazolopyrimidine 1 using N-iodosuccinimide as an iodinating agent. The synthesis of compound 2 started with nucleophilic substitution of 3-iodo-1H-pyrazolo [3,4-d]pyrimidin-4-amine with R-X (X:-OMs, -Br, -Cl), affording N-alkylated pyrazolo [3,4-d]pyrimidine. We performed this synthesis using a weak inorganic base and the mild temperature was also used for a two-step procedure to generate N-alkylated pyrazolo [3,4-d]pyrimidine derivatives. Also, all compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and the human carbonic anhydrase (hCA) isoforms I and II, with K i values in the range of

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Porous Catalytic Systems in the Synthesis of Bioactive Heterocycles and Related Compounds

Pérez‐Mayoral

Casilda

Godino

et al. 2015

Green Synthetic Approaches for Biologically Relevant Heterocycles

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Experimental and theoretical study of pyrazole N-alkylation catalyzed by basic modified molecular sieves

Cited by 16 publications

References 40 publications

Pyrimidines: Molecular docking and inhibition studies on carbonic anhydrase and cholinesterases

Pyrimidines: Molecular docking and inhibition studies on carbonic anhydrase and cholinesterases

Synthesis of N‐alkylated pyrazolo[3,4‐d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties

Porous Catalytic Systems in the Synthesis of Bioactive Heterocycles and Related Compounds

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