[Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity].
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.
Ando
Kumiko
K
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. kumikoan@mwu.mukogawa-u.ac.jp
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D008968:Molecular Conformation; D009504:Neutrophils / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005663:Furans; C513240:LTB4R protein, human; C485878:LTB4R2 protein, human; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D013929:Thromboxane B2; D002118:Calcium