title: Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ando
authors.forename: Eriko
authors.initials: E
authors.lastname: Tsuji
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ando
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kunitomo
authors.forename: Reina
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Ohta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabe
authors.forename: Shigekatsu
authors.initials: S
authors.lastname: Kohno
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohishi
mesh_terms: 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
chemical_list: D001572:Benzofurans; D018102:Receptors, Leukotriene B4