Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors

Orjales, A.; Mosquera, Ricardo A.; López, Beatriz; Olivera, Roberto; Labeaga, Luis; Nunez, M. T.

doi:10.1016/j.bmc.2007.11.079

Cited by 51 publications

(55 citation statements)

References 52 publications

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“…Table 1. Substitutional variations of 2-(4-methylsulphonylphenyl)-pyrimidine derivatives (see Figure 1 for general structure and reference [34] In all, the number of compounds (n) is 46, r is the correlation coefficient, QThus a lower value of descriptors Ss and Se and a higher value of descriptors Mv and Mp would be favourable to the activity. The descriptors X0Av and Rww are topological descriptors.…”

Section: Qsar Resultsmentioning

confidence: 99%

“…The study has involved a chemical structure database of 2-(4-methylsulphonylphenyl)pyrimidine derivatives ( Figure 1), reported by Orjales et al 34 The general structure of these derivatives has been given in Figure 1. The substitutional variations at different positions of the generalized structure are shown in Table 1.…”

Section: Dataset and Molecular Descriptorsmentioning

confidence: 99%

“…Moreover, the traditional NSAIDs are not devoid of toxic effects on cardiovascular system 32,33 . As a further development in COX-2 inhibitors, recently a series of pyrimidine derivatives has been reported as potent and highly selective ones 34 . In view of the importance of anti-inflammatory agents in the clinical management of several disorders, a quantitative structure-activity relationship is attempted on the COX-2 inhibition activity of these pyrimidine derivatives.…”

Section: Introductionmentioning

confidence: 99%

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QSAR of 2-(4-methylsulphonylphenyl)pyrimidine derivatives as cyclooxygenase-2 inhibitors: simple structural fragments as potential modulators of activity

Sharma

Singh

Pilania

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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Section: Qsar Resultsmentioning

confidence: 99%

Section: Dataset and Molecular Descriptorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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QSAR of 2-(4-methylsulphonylphenyl)pyrimidine derivatives as cyclooxygenase-2 inhibitors: simple structural fragments as potential modulators of activity

Sharma

Singh

Pilania

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…DHPMs are also used as orally active antihypertensive agents [10,11] , as α1a adrenoceptor selective antagonists [12] and cyclooxygenase-2 inhibitors [13] . The batzelladine alkaloids A and B are used for the treatment of the epidemic, acquired immune deficiency syndrome (AIDS), which inhibited the binding of human immunodeficiency virus envelope protein gp-120 to human CD4 cells to become potential new leads for AIDS therapy [14] .…”

Section: Research Papermentioning

confidence: 99%

“…Proton at ethylene group linkage at C-23 shown δ= 6.98 ppm as singlet. Looking to the 13 C NMR spectra, values of the chemical shift of final compound 4c was observed in between the range of δ= 167.1-13.8 ppm. In the carbon of methyl groups of at C-8 and C-22 appeared at δ= 16.2 and 13.8 ppm, respectively.…”

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confidence: 99%

Synthesis and Antimicrobial Activity of Fluorine Containing Pyrazole-clubbed Dihydropyrimidinones

Desai¹,

Vaghani²,

Patel³

et al. 2018

pharmaceutical-sciences

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Desai, et al.: Fluorine Containing Pyrazole-clubbed DihydropyrimidinonesIn the present communication synthesis of pyrazole-containing dihydropyrimidinone motifs (4a-o) and their antimicrobial activity and cytotoxicity were reported. The newly synthesized compounds were characterized using infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and mass spectral techniques. Compounds 4b, 4c, 4f, 4g, 4i and 4j were the most active derivatives identified during antimicrobial activity screening. On the basis of antibacterial activities, it was observed that compounds 4b and 4c exhibited activity against methicillin resistant Staphylococcus aureus with minimum inhibitory concentrations of 12.5 and 6.25 µg/ml, respectively. From structure activity relationship studies, it could be concluded that electron withdrawing groups played a crucial role in enhancing antimicrobial and cytotoxic effects of title compounds. In addition, the results of the cytotoxicity studies indicated that compounds 4b, 4c, 4g and 4j possessed lower levels of cytotoxicity.

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Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Sahu

Siddiqui

Naim

et al. 2017

Archiv der Pharmazie

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A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED ), 285.02 and 293.42 mg/kg (scPTZ ED ), and 389.11 and 412.16 mg/kg (TD ), respectively. Docking studies were also performed for all synthesized compounds to get insight into the binding pattern toward the GABA receptor as a possible mechanism of their anticonvulsant action, and in silico ADME studies were carried out to predict the safety and stability of the molecules. The increased GABA level in the experimental animals in the neurochemical estimation assay confirmed their GABAergic modulating activity. The most potent compounds were also evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a broad spectrum of anticonvulsant activity with a large safety margin. Together, this research suggested that 4o and 4s may serve as leads in the discovery and development of new anticonvulsant drugs.

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Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors

Cited by 51 publications

References 52 publications

QSAR of 2-(4-methylsulphonylphenyl)pyrimidine derivatives as cyclooxygenase-2 inhibitors: simple structural fragments as potential modulators of activity

QSAR of 2-(4-methylsulphonylphenyl)pyrimidine derivatives as cyclooxygenase-2 inhibitors: simple structural fragments as potential modulators of activity

Synthesis and Antimicrobial Activity of Fluorine Containing Pyrazole-clubbed Dihydropyrimidinones

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

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