<p>A series of novel compounds phosphoryl-containing polyunsaturated fatty acid derivatives <i>n</i>-(diisopropoxy-phosphonamide)-alkyl ester (<b>2a–2o</b>) have been synthesized and evaluated for lowering hypolipidemia activities. Amongst all the synthesized compounds, compound <b>2d, 2h</b>, and <b>2m</b> showed significant lowering of triglyceride (TG) by 47.37%, 45.88%, and 45.69%, respectively, in triton induced hyperlipidemic in mice. Furthermore, compound <b>2d</b> showed potent antihyperlipidemic activity and was found to decrease the plasma total cholesterol levels (TC) by 53.3%, TG by 29.3%, in high-fat diet induced hyperlipidemic in mice.</p
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