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Synthesis and biologic evaluation of new 3-phenoxyazetidin-2-one derivatives as selective cyclooxygenase-2 inhibitors

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Abstract

A new series of 3-phenoxyazetidin-2-ones (β-lactams) were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the 0.054–0.095 μM range, and COX-2 selectivity indexes in the 228.47–355.6 range. Among the synthesized compounds, 1-(4-methoxyphenyl)-4-(4-(methylsulfonyl)phenyl)-3-phenoxyazetidin-2-one (4j) possessing methoxy group at the para position of N-1 phenyl ring exhibited the highest COX-2 inhibitory selectivity and potency even more potent than the reference drug celecoxib. Molecular modeling studies indicated that the methylsulfonyl pharmacophore group can be inserted into the secondary pocket of COX-2 active site.

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Acknowledgments

We like to thank Deputy of Research, School of Pharmacy, Shahid Beheshti University of Medical Sciences, for financial support of this work as part of Ph.D thesis of Hadi Arefi.

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  1. Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box 14155-6153, Tehran, Iran

    H. Arefi & A. Zarghi

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  1. H. Arefi
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  2. A. Zarghi
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Correspondence to A. Zarghi.

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Arefi, H., Zarghi, A. Synthesis and biologic evaluation of new 3-phenoxyazetidin-2-one derivatives as selective cyclooxygenase-2 inhibitors. Med Chem Res 22, 3881–3887 (2013). https://doi.org/10.1007/s00044-012-0387-1

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  • DOI: https://doi.org/10.1007/s00044-012-0387-1

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