- Isomeric methoxy analogs of nimesulide for development of brain cyclooxygense-2 (COX-2)-targeted imaging agents: Synthesis, in vitro COX-2-inhibitory potency, and cellular transport properties
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Nimesulide analogs bearing a methoxy substituent either at the ortho-, meta- or para-position on the phenyl ring, were designed, synthesized, and evaluated for potential as radioligands for brain cyclooxygenase-2 (COX-2) imaging. The synthesis of nimesulide and regioisomeric methoxy analogs was based on the copper-mediated arylation of phenolic derivatives for the construction of diaryl ethers. These isomeric methoxy analogs displayed lipophilicity similar to that of nimesulide itself, as evidenced by their HPLC log P7.4 values. In vitro inhibition studies using a colorimetric COX (ovine) inhibitor-screening assay demonstrated that the para-methoxy substituted analog retains the inhibition ability and selectivity observed for parent nimesulide toward COX-2 enzyme, whereas the meta- and ortho-methoxy substituents detrimentally affected COX-2-inhibition activity, which was further supported by molecular docking studies. Bidirectional transport cellular studies using Caco-2 cell culture model in the presence of the P-glycoprotein (P-gp) inhibitor, verapamil, showed that P-gp did not have a significant effect on the efflux of the para-methoxy substituted analog. Further investigations using the radiolabeled form of the para-methoxy substituted analog is warranted for in vivo characterization.
- Yamamoto, Yumi,Hisa, Takuya,Arai, Jun,Saito, Yohei,Yamamoto, Fumihiko,Mukai, Takahiro,Ohshima, Takashi,Maeda, Minoru,Ohkubo, Yasuhito
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p. 6807 - 6814
(2015/11/11)
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- 4-NITRO-2- (4 -METHOXY)-PHENOXY -METHANESULFONANILIDE DERIVATES AND THEIR PHARMACEUTICAL USE
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The present invention discloses 4-nitro-2-[(4'methoxy)-phenoxy] -methanesulfonyl aniline, or pharmaceutically acceptable salts, solvates or hydrates thereof, or mixtures thereof with povidone, phospholipid or cyclodextrin, and their pharmaceutical uses, e
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Page/Page column 5
(2008/06/13)
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- A total synthesis of 4-hydroxynimesulide
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4-Hydroxynimesulide, a unique metabolite of Nimesulide has been synthesized by the formation of 4-methoxynimesulide and its subsequent demethylation with aq. HBr-AcOH/anhyd. AlCl3-CH2Cl2.
- Singh, Parmjeet,Singh, Amarjit,Sharma
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p. 1263 - 1264
(2007/10/03)
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