Lazer E S, Wong H C, Possanza G J, Graham A G, Farina P R
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
J Med Chem. 1989 Jan;32(1):100-4. doi: 10.1021/jm00121a021.
A series of 2,6-di-tert-butyl-4-(2-arylethenyl)phenols was prepared and examined for their ability to inhibit cyclooxygenase and 5-lipoxygenase in vitro and developing adjuvant arthritis in vivo in the rat. Structure-activity relationships are discussed. Among the best compounds is (E)-2,6-di-tert-butyl-4-[2-(3-pyridinyl)ethenyl]phenol (7d). It has an IC50 of 0.67 microM for cyclooxygenase and 2.7 microM for 5-lipoxygenase and an ED50 of 2.1 mg/kg in developing adjuvant arthritis. Additional in vivo data are reported for 7d.
制备了一系列2,6 - 二叔丁基 - 4 -（2 - 芳基乙烯基）苯酚，并检测了它们在体外抑制环氧化酶和5 - 脂氧合酶的能力以及在大鼠体内抑制佐剂性关节炎发展的能力。讨论了构效关系。其中最佳化合物为（E）-2,6 - 二叔丁基 - 4 - [2 -（3 - 吡啶基）乙烯基]苯酚（7d）。它对环氧化酶的IC50为0.67微摩尔，对5 - 脂氧合酶的IC50为2.7微摩尔，在佐剂性关节炎发展中的ED50为2.1毫克/千克。还报告了7d的其他体内数据。
