Buckle D R, Rockell C J, Smith H, Spicer B A
J Med Chem. 1986 Nov;29(11):2262-7. doi: 10.1021/jm00161a022.
Several N-benzylpiperazino derivatives of [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-one and its 5-methyl homologue have been prepared and evaluated for H1-antihistamine activity on guinea pig ileum. The most potent compounds were also evaluated for their ability to stabilize mast cells in the rat passive peritoneal anaphylaxis (PPA) system and were shown to inhibit histamine release at concentrations below those required to inhibit extravasation, suggesting that this might be relevant to their antianaphylactic activity in this system. The compound tested with the most potent H1-antihistamine activity was 6-[3-[4-(4-chlorobenzyl)-1-piperazinyl]propoxy][1]benzopyrano[2,3- d]-1,2,3-triazol-9(1H)-one, 28, which had a pA2 of 9.1 against histamine on guinea pig ileum, comparable to that of mepyramine, and inhibited histamine release in the rat PPA system with an IC50 value of 5.4 X 10(-6) M.
已经制备了[1]苯并吡喃并[2,3-d]-1,2,3-三唑-9(1H)-酮及其5-甲基同系物的几种N-苄基哌嗪衍生物，并在豚鼠回肠上评估了它们的H1-抗组胺活性。还评估了最有效的化合物在大鼠被动腹膜过敏反应（PPA）系统中稳定肥大细胞的能力，结果表明它们在低于抑制血管外渗所需浓度时就能抑制组胺释放，这表明这可能与其在该系统中的抗过敏活性有关。具有最强H1-抗组胺活性的测试化合物是6-[3-[4-(4-氯苄基)-1-哌嗪基]丙氧基][1]苯并吡喃并[2,3-d]-1,2,3-三唑-9(1H)-酮（28），其对豚鼠回肠组胺的pA2为9.1，与美吡拉敏相当，并且在大鼠PPA系统中抑制组胺释放的IC50值为5.4×10(-6) M。
