Synthesis of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives as potent anti-inflammatory agents and inhibitors of monocyte-to-macrophage transformation

• Novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ethers.
• Compound 7e, 7f, 7h, 9b, 9d, 9e, 9h showed impressive anti-inflammatory activity.
• Compound 9h significantly inhibited PMA-induced MMP-9 gelatinase activity by 75%.
• 9e and 9h greatly inhibited the PMA-induced monocyte-to-macrophage transformation.

A series of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives 7a–h and 9a–h were synthesized starting from sodium salt of saccharin 1 in series of steps. Final compounds 7a–h and 9a–h were evaluated for the anti-inflammatory activity and their ability to inhibit monocyte-to-macrophage transformation. Compounds 7e, 9b, 9e and 9h showed impressive anti-inflammatory activities (TNF-α, IL-8 and MCP-1) at micro molar concentration which was found to be better than positive control i.e., piroxicam. Compound 9e marginally and compound 9h significantly inhibited PMA-induced MMP-9 gelatinase activity. Also compounds 9e and 9h greatly inhibited the PMA-induced monocyte-to-macrophage transformation, a pre-requisite step in the formation of atheroma.

Novel 1,2-benzothiazine derivatives 7a–h and 9a–h were synthesized, evaluated for anti-inflammatory and monocyto-to-macrophage inhibition activity. Compounds 9e and 9h greatly inhibited the PMA-induced MMP-9 gelatinase activity and monocyte-to-macrophage transformation.Figure optionsDownload as PowerPoint slide