Ando Kumiko
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Yakugaku Zasshi. 2005 Nov;125(11):863-74. doi: 10.1248/yakushi.125.863.
Variable 7-carboxylpropoxy or (1-phenyl)ethoxybenzo[b]furan derivatives with (E)- and (Z)-2-alkylcarbamoyl-1-methylvinyl groups at the 2-, 4-, and 5-positions were prepared to find novel and selective leukotriene B(4) (LTB(4)) receptor antagonists. (E)-2-(2-Diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4v) showed selective inhibition of the human BLT(2) receptor (hBLT(2)). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (7c) inhibited both human BLT(1) receptor (hBLT(1)) and hBLT(2). 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 a torsion angle (45.7 degrees ) 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-alkylcarbamoyl-1-methylvinyl groups.
制备了在2-、4-和5-位带有（E）-和（Z）-2-烷基氨基甲酰基-1-甲基乙烯基的可变7-羧基丙氧基或（1-苯基）乙氧基苯并[b]呋喃衍生物，以寻找新型的选择性白三烯B4（LTB4）受体拮抗剂。（E）-2-（2-二乙基氨基甲酰基-1-甲基乙烯基）-7-（1-苯乙氧基）苯并[b]呋喃（4v）对人BLT2受体（hBLT2）表现出选择性抑制作用。另一方面，（E）-2-乙酰基-4-（2-二乙基氨基甲酰基-1-甲基乙烯基）-7-（1-苯乙氧基）苯并[b]呋喃（7c）对人BLT1受体（hBLT1）和hBLT2均有抑制作用。（E）-2-（2-二乙基氨基甲酰基-1-甲基乙烯基）基团与苯并[b]呋喃环大致处于同一平面，而（E）-4-（2-二乙基氨基甲酰基-1-甲基乙烯基）基团与苯并[b]呋喃环平面的扭转角为45.7°。然而，（Z）-（2-烷基氨基甲酰基-1-甲基乙烯基）苯并[b]呋喃没有活性。抑制活性取决于2-烷基氨基甲酰基-1-甲基乙烯基基团的构象。
