Design, synthesis, and biological evaluation of 3,4,5-trimethoxyphenyl acrylamides as antinarcotic agents

Abstract

The synthesis and biological evaluation of 3,4,5-trimethoxyphenyl acrylamides 1a–f as novel antinarcotic agents are described. The molecules were prepared by the Wittig reaction, followed by a coupling reaction between 3,4,5-trimethoxycinnamic acid (9) and aliphatic amines, which resulted in good yields. When tested for biological activity, compounds 1d–f exhibited strong inhibitory effects on the morphine withdrawal syndrome in mice due to their high binding affinities with serotonergic 5-HT_1A receptors.

Keywords::

• 3;4;5-trimethoxyphenyl acrylamides
• antinarcotic activity
• morphine withdrawal syndrome
• Wittig reaction
• coupling synthesis

Acknowledgments

This work was supported by Ewha Global Challenge (BK21), a KFDA grant (2008), and a Korean Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-312-C00267), the Republic of Korea. Two of the authors (D.M. and Y.L.) appreciate the fellowship of the BK21 program from the Ministry of Education and Human Resources Development. The first two authors (J.-C.J. and D.M.) contributed equally to this work.