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image of Design, Synthesis and Biological Evaluation of New 4-(4-(Methylsulfonyl)Phenyl)-6-Phenylpyrimidin-2-Amine Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors

Abstract

Introduction

Cyclooxygenase, an enzyme that occurs in at least two distinct variants ( and ), is the target of classical inhibitors, which lack selectivity and inhibit both types of . However, a recent approach focuses explicitly on inhibiting , commonly found in inflamed tissue, resulting in fewer adverse effects than inhibitors.

Methods

A series of 4-(4-(methylsulfonyl)phenyl)-6-phenylpyrimidin-2-amine derivatives were synthesized through a two-step process. First, 4-substituted acetophenones underwent base-catalyzed Claisen-Schmidt condensation with 4-(methylsulfonyl)benzaldehyde to yield chalcones, which were then cyclized with guanidine hydrochloride under basic reflux conditions. Molecular docking was performed using AutoDock Vina software. The inhibitory activities of and were evaluated using enzymatic assays. Antiplatelet aggregation was measured a turbidimetric method, and antiproliferative activity was assessed using the MTT assay.

Results

The experiments on inhibition revealed that a substantial number of the synthesized compounds presented a strong suppressive effect against . The assessment of antiplatelet aggregation activity indicated that most of the derivatives effectively inhibited ADP-induced platelet aggregation. Compound exhibited the most potent antiproliferative activity, comparable to cisplatin. The docking studies and molecular modeling results demonstrated that the designed compounds, except for , exhibited a binding behavior comparable to that of celecoxib. In addition, the insertion of the SOMe moiety within the secondary binding site of was observed.

Discussion

These findings suggest that the structural modifications introduced in the synthesized derivatives contribute significantly to their selective inhibition and antiplatelet properties. The correlation between docking results and biological assays supports the rationale behind the design of the compound.

Conclusion

The 4-(4-(methylsulfonyl)phenyl)-6-phenylpyrimidin-2-amine exhibits unique properties as a inhibitor, displaying effective inhibition of while showing minimal interaction with the enzyme. Furthermore, our study revealed that most of these compounds exhibited inhibitory effects on ADP-induced platelet aggregation.

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2025-07-16
2025-09-26

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Design, Synthesis and Biological Evaluation of New 4-(4-(Methylsulfonyl)Phenyl)-6-Phenylpyrimidin-2-Amine Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors
Bentham Science Publishers ; https://doi.org/10.2174/0118715206380378250709112246
/content/journals/acamc/10.2174/0118715206380378250709112246
/content/journals/acamc/10.2174/0118715206380378250709112246
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  • Article Type:     Research Article
Keywords: 4-(4-(methylsulfonyl)phenyl)-6-phenylpyrimidin-2-amine ; molecular modeling ; platelet aggregation inhibitors ; chalcone ; cytotoxic activity ; COX enzyme

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