選択的LTB_4受容体阻害活性を有する2-Alkylcarbamoyl-1-methylvinylbenzo[b]furan誘導体の合成とそのコンプォメーション

摘要

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-l -methylvinyl)-7- (1-phenylethoxy)benzo [b] furan (7c) inhibited both human BLTj receptor (hBLT]) and hBLT_2.The (E) -2-(2-diethylcarbamoyl-l-methylvinyl) group lay on approximately the same plane as the benzo [b] furan ring,whereas the (E)-4-(2-diethylcarbamoyl-l-methylvinyl) group had a torsion angle (45.7deg) from the benzo [b] furan ring plane.However,the (Z)-(2-alkylcarbamoyl-l-methylvinyl) benzo [b] furans were inactive. The inhibitory activity depended on the conformation of the 2-alkylcarbamoyl-l-methylvinyl groups.