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°) 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.
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