- A novel combination of (diacetoxyiodo)benzene and tert-butylhydroperoxide for the facile oxidative dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones
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A clean and efficient oxidative dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones to 1,2-dihydropyrimidines has been achieved through a novel combination of (diacetoxyiodo)benzene and tert-butylhydroperoxide in CH2Cl2.
- Karade, Nandkishor N.,Gampawar, Sumit V.,Kondre, Jeevan M.,Tiwari, Girdharilal B.
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- Discovery of new phenyl sulfonyl-pyrimidine carboxylate derivatives as the potential multi-target drugs with effective anti-Alzheimer's action: Design, synthesis, crystal structure and in-vitro biological evaluation
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Alzheimer's disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. All the synthesized compounds were validated by 1HNMR, 13CNMR, HRMS, and BS-19 were structurally validated by X-Ray single diffraction analysis. To evaluate the plausible binding affinity of designed compounds, molecular docking study was performed, and the result revealed their significant interaction with active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The synthesized compounds displayed moderate to excellent in vitro enzyme inhibitory activity against AChE and BuChE at nanomolar (nM) concentration. Among 24 compounds (BS-1 to BS-24), the optimal compounds (BS-10 and BS-22) displayed potential inhibition against AChE; IC50 = 47.33 ± 0.02 nM and 51.36 ± 0.04 nM and moderate inhibition against BuChE; IC50 = 159.43 ± 0.72 nM and 153.3 ± 0.74 nM respectively. In the enzyme kinetics study, the compound BS-10 displayed non-competitive inhibition of AChE with Ki = 8 nM. Respective compounds BS-10 and BS-22 inhibited AChE-induced Aβ1-42 aggregation in thioflavin T-assay at 10 μM and 20 μM, but BS-10 at 10 μM and 20 μM concentrations are found more potent than BS-22. In addition, the aggregation properties were determined by the dynamic light scattering (DLS) and was found that BS-10 and BS-22 could significantly inhibit self-induced as well as AChE-induced Aβ1-42 aggregation. The effect of compounds (BS-10 and BS-22) on the viability of MC65 neuroblastoma cells and their capability to cross the blood-brain barrier (BBB) in PAMPA-BBB were further studied. Further, in silico approach was applied to analyze physicochemical and pharmacokinetics properties of the designed compounds via the SwissADME and PreADMET server. Hence, the novel phenylsulfonyl-pyrimidine carboxylate derivatives can act as promising leads in the development of AChE inhibitors and Aβ disaggregator for the treatment of AD.
- Manzoor, Shoaib,Prajapati, Santosh Kumar,Majumdar, Shreyasi,Raza, Kausar,Gabr, Moustafa T.,Kumar, Shivani,Pal, Kavita,Rashid, Haroon,Kumar, Suresh,Krishnamurthy, Sairam,Hoda, Nasimul
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- Acridone-pyrimidine hybrids- design, synthesis, cytotoxicity studies in resistant and sensitive cancer cells and molecular docking studies
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Hybrid systems of acridones with substituted pyrimidines were designed with an objective of discovering next generation anticancer agents targeting multiple mechanisms in the cancer cell. Hybrid compounds were synthesized by simple and convenient methods
- Murahari, Manikanta,Prakash, Karanam Vanitha,Peters, Godefridus J.,Mayur
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p. 961 - 981
(2017/09/08)
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- Free-radical oxidation of 1,2,3,4-tetrahydro-2-oxopyrimidines
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Free-radical oxidation of 4-substituted 5-acetyl-and 5-carboethoxy-1,2,3,4- tetrahydro-2-oxopyrimidines using benzoyl peroxide under thermal conditions has been investigated to elucidate the effects of the nature of the substituents in the 4- and 5-positi
- Memarian, Hamid Reza,Jafarpour, Nazanin,Farhadi, Asadallah
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experimental part
p. 277 - 281
(2012/07/02)
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