Ilhan M, Long J P, Flynn J, Bhatnagar R, Cannon J G
Arch Int Pharmacodyn Ther. 1984 Sep;271(1):22-32.
Dopamine receptor agonist activity was evaluated using resorcinol derivatives of the following ring systems: dopamine, aminotetralin, indan, benzocycloheptane, octahydrobenzo(f)quinoline and octahydrobenzo[g]quinoline. The compounds were evaluated for biological activity using in vitro binding assays, anesthetized cat blood pressure and heart rate, cat cardioaccelerator nerve preparation and rotations of rats with unilateral denervation of the caudate nucleus. Resorcinol substitutions were chosen because one hydroxyl group corresponded to the alpha-conformer of dopamine and the second hydroxyl group corresponded to the beta-conformer of dopamine. Dopamine receptor activity was found primarily with derivatives of aminotetralin and octahydrobenzo[f]quinoline while the other ring systems yielded compounds which were quite inactive. The active resorcinol derivatives were found in the same ring systems where catechol substitution was active in ring positions corresponding to either the alpha- or beta-conformer of dopamine. Likewise in those ring systems where catechol substitution corresponding to the beta-conformer of dopamine were quite inactive, resorcinol substitution in these series was not favorable for activity. The ring systems requirements for alpha- and beta-adrenoceptor agonist activity did not follow the same structural pattern as found for dopamine receptor agonist activity.
多巴胺、氨基四氢萘、茚满、苯并环庚烷、八氢苯并[f]喹啉和八氢苯并[g]喹啉。使用体外结合试验、麻醉猫的血压和心率、猫心脏加速神经制备以及单侧尾状核去神经大鼠的旋转来评估这些化合物的生物活性。选择间苯二酚取代基是因为一个羟基对应多巴胺的α-构象体，第二个羟基对应多巴胺的β-构象体。主要在氨基四氢萘和八氢苯并[f]喹啉的衍生物中发现多巴胺受体活性，而其他环系产生的化合物活性相当低。活性间苯二酚衍生物存在于与多巴胺的α-或β-构象体相对应的环位置上儿茶酚取代具有活性的相同环系中。同样，在那些与多巴胺的β-构象体相对应的儿茶酚取代相当不活跃的环系中，这些系列中的间苯二酚取代不利于活性。α-和β-肾上腺素能受体激动剂活性的环系要求与多巴胺受体激动剂活性的结构模式不同。
