Design, synthesis, and biological evaluation of  3,4,5-trimethoxyphenyl acrylamides as antinarcotic agents.
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-HT1A receptors.
Jung
Jae-Chul
JC
Department of Neuroscience and Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, Korea.
Min
Dongguk
D
Kim
Heejeong
H
Jang
Soyong
S
Lee
Yongnam
Y
Park
WooKyu
W
Khan
Ikhlas A
IA
Moon
Hyung-In
HI
Jung
Mankil
M
Oh
Seikwan
S
D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization
D000178:Acrylamides; D009292:Narcotic Antagonists; D044282:Receptor, Serotonin, 5-HT1A