Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity.
Variable benzo[b]furan derivatives having (E)- and (Z)-2-alkylcarbamoyl-1-methylvinyl groups at the 2-, 4- and 5-positions and a carboxylpropoxy or (1-phenyl)ethoxy group at the 7-position were prepared to find novel and selective leukotriene B4(LTB4) receptor antagonists. (E)-2-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4v) showed selective inhibition to the human BLT2 receptor (hBLT2). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (7v) inhibited both human BLT(1) receptor (hBLT1) and hBLT2. The (E)-2-(2-diethylcarbamoyl-1-methylvinyl) group lay on approximately the same plane as the benzo[b]furan ring, whereas the (E)-4-(2-diethylcarbamoyl-1-methylvinyl) group had the torsion angle (45.7 degree) from the benzo[b]furan ring plane. However, the (Z)-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans were inactive. The inhibitory activity depended on the conformation of the 2-diethylcarbamoyl-1-methylvinyl group.
Ando
Kumiko
K
School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan.
Tsuji
Eriko
E
Ando
Yuko
Y
Kunitomo
Jun-ichi
J
Kobayashi
Reina
R
Yokomizo
Takehiko
T
Shimizu
Takao
T
Yamashita
Masayuki
M
Ohta
Shunsaku
S
Nabe
Takeshi
T
Kohno
Shigekatsu
S
Ohishi
Yoshitaka
Y
D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization
D001572:Benzofurans; D018102:Receptors, Leukotriene B4