McDermed J D, McKenzie G M, Freeman H S
J Med Chem. 1976 Apr;19(4):547-9. doi: 10.1021/jm00226a021.
In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.
为了进一步确定中枢多巴胺受体激动剂的结构要求，合成了已知激动剂5,6 - 二羟基 - 2 - 二丙基氨基 - 1,2,3,4 - 四氢萘的一些单羟基类似物。对它们进行了犬催吐作用和大鼠刻板行为的检测。最有效的是5 - 羟基 - 2 - 二丙基氨基 - 1,2,3,4 - 四氢萘，其效力比阿扑吗啡强，但比二羟基类似物弱。单羟基类似物的两种对映体通过常规方法从光学活性中间体2 - 苄基氨基 - 5 - 甲氧基 - 1,2,3,4 - 四氢萘合成。该胺的拆分借助扁桃酸进行。发现多巴胺能活性仅限于左旋对映体。发现四氢萘类化合物中取代和手性的要求与多巴胺能阿朴啡类化合物已知的要求密切对应。
