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 B-4 (LTB4) receptor antagonists. ( E)- 2-( 2- Diethylcarbamoyl-1-methylvinyl)-7( 1- phenylethoxy) benzo[ b] furan ( 4v) showed selective inhibition to the human BLT2 receptor (hBLT(2)). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy) benzo[ b] furan (7v) inhibited both human BLT1 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 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-diethylcarbamoyl-1-methylvinyl group.