Matsumoto K, Stark P, Meister R G
J Med Chem. 1977 Jan;20(1):17-24. doi: 10.1021/jm00211a004.
A series of 1-amino- and 1-mercapto-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyrans was synthesized and subsequently evaluated in three rodent test systems for CNS activity. The structure-activity data generated indicate that, in general, a change of the 1-hydroxy group to an amine results in a retention of pharmacological activity but that a change to sulfur results in loss of pharmacological activity. Derivatization of the 1-amino group with various functions decreased the activity of the parent compound. For optimum potency, in all series, the 3-position alkyl side chain should be either 1,1- or 1,2-dimethylheptyl. With either the 1-hydroxy- or 1-amino-7,8,9,10-tetrahydro-3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (4c or 10c), preparation of the optically active antipodes did not lead to any great degree of spearation of activity. Both of the antipodes possess pharmacological activity as measured in these rodent test systems.
合成了一系列1-氨基-和1-巯基-7,8,9,10-四氢-6H-二苯并[b,d]吡喃，并随后在三种啮齿动物试验系统中评估其对中枢神经系统的活性。所产生的构效关系数据表明，一般来说，将1-羟基换成胺会保留药理活性，但换成硫则会导致药理活性丧失。用各种官能团对1-氨基进行衍生化会降低母体化合物的活性。为了达到最佳效力，在所有系列中，3-位烷基侧链应为1,1-或1,2-二甲基庚基。对于1-羟基-或1-氨基-7,8,9,10-四氢-3-(1,1-二甲基庚基)-6,6,9-三甲基-6H-二苯并[b,d]吡喃（4c或10c），制备旋光对映体并未导致活性有很大程度的分离。在这些啮齿动物试验系统中测定时，两种对映体均具有药理活性。
