Soll R M, Humber L G, Deininger D, Asselin A A, Chau T T, Weichman B M
J Med Chem. 1986 Aug;29(8):1457-60. doi: 10.1021/jm00158a023.
The synthesis of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole (7) is described. Compound 7 was tested for analgesic properties in the phenylbenzoquinone writhing test and was found to be essentially devoid of activity. In contrast, cis-3-[4-(2-heptyloxy)-2-hydroxyphenyl]cyclohexanol (8), the analogue in which the pyrrolo ring is replaced by a hydroxyl group, had an ED50 of 8.3 mg/kg, sc, in the same model. The absence of bioisosterism between the pyrrolo ring and the phenolic hydroxyl group, in this instance, is discussed in terms of the circumstances that control the manifestation of bioisofunctionality between a pyrrolo ring and a phenolic hydroxyl group, which functions as a hydrogen-bond donor.
本文描述了4-(2-庚氧基)-7-[(Z)-(3-羟基环己基)]吲哚(7)的合成。在苯醌扭体试验中对化合物7的镇痛特性进行了测试，结果发现其基本没有活性。相比之下，顺式-3-[4-(2-庚氧基)-2-羟基苯基]环己醇(8)，即吡咯环被羟基取代的类似物，在同一模型中的皮下给药半数有效剂量(ED50)为8.3mg/kg。本文根据控制吡咯环和作为氢键供体的酚羟基之间生物异功能表现的情况，讨论了在这种情况下吡咯环和酚羟基之间不存在生物电子等排体的情况。
