Kamenka J M, Chiche B, Goudal R, Geneste P, Vignon J, Vincent J P, Lazdunski M
J Med Chem. 1982 Apr;25(4):431-5. doi: 10.1021/jm00346a019.
The following monohydroxy derivatives of 1-(1-phenylcyclohexyl)piperidine (phencyclidine, PCP) were synthesized: o-, m-, and p-phenols of PCP, 1-(1-phenylcyclohexyl)-4-piperidinol, and two stereoisomeric pairs of 3-phenyl-3-(1-piperidinyl)cyclohexanol and 4-phenyl-4-(1-piperidinyl)cyclohexanol. Inhibition of specific binding of tritiated PCP, morphine, or quinuclidinyl benzylate (QNB) in rat brain homogenates was measured for these compounds. Inhibition of PCP binding for selected compounds correlated with mouse rotarod assay activity. The most characteristic effects of hydroxylation of PCP on the cyclohexyl, piperidine, or phenyl moieties are the following: (i) it generally decreases its activity in inhibiting [3H]PCP binding by a factor of 10 to 80; (ii) it does not produce a large variation in the affinity for the morphine receptor; (iii) it produces a considerable decrease of the affinity for the muscarinic receptor. An important exception to these general observations was the metaphenolic derivative of PCP. This PCP derivative has an affinity for the [3H]PCP binding sites that is 8 times higher than that of PCP itself; its affinity for the muscarinic receptor is only twice lower than that of PCP, but its affinity for the morphine receptor is 430 times higher than that of PCP and only one order of magnitude lower than that of morphine itself.
合成了以下1-(1-苯基环己基)哌啶（苯环利定，PCP）的单羟基衍生物：PCP的邻、间、对苯酚，1-(1-苯基环己基)-4-哌啶醇，以及3-苯基-3-(1-哌啶基)环己醇和4-苯基-4-(1-哌啶基)环己醇的两对立体异构体。测定了这些化合物对大鼠脑匀浆中氚标记的PCP、吗啡或喹核醇基苯甲酸酯（QNB）特异性结合的抑制作用。所选化合物对PCP结合的抑制作用与小鼠转棒试验活性相关。PCP在环己基、哌啶基或苯基部分羟基化的最显著影响如下：（i）它通常会使其抑制[3H]PCP结合的活性降低10至80倍；（ii）它对吗啡受体的亲和力没有产生很大变化；（iii）它使对毒蕈碱受体的亲和力显著降低。这些一般观察结果的一个重要例外是PCP的间酚衍生物。这种PCP衍生物对[3H]PCP结合位点的亲和力比PCP本身高8倍；它对毒蕈碱受体的亲和力仅比PCP低两倍，但它对吗啡受体的亲和力比PCP高430倍，仅比吗啡本身低一个数量级。
