McQuinn R L, Cone E J, Shannon H E, Su T P
J Med Chem. 1981 Dec;24(12):1429-32. doi: 10.1021/jm00144a011.
In order to investigate the structural requirements for a cycloalkyl moiety in the potent hallucinogen 1-(1-phenylcyclohexyl)piperidine (PCP, 1), a series of structural analogues was synthesized in which the size of the cycloalkyl ring was varied from three carbons to eight carbons. Biological activities of these compounds were assessed in an in vitro assay (phencyclidine binding assay) and an in vivo assay (discriminative stimulus assay). As the cycloalkyl ring size decreased from that of cyclohexane (PCP), PCP-like activity declined in both assays, but as the cycloalkyl ring size became larger than cyclohexane, a sharp decline in PCP-like activity was observed in the in vivo assay, while activity in the in vitro assay was only slightly less than that of PCP. 1-(1-Phenylcyclooctyl)piperidine (8) had potent competitive binding properties in the in vitro binding assay but produced no observable PCP-like effects in the in vivo assay. The importance of the cycloalkyl ring in the structure of PCP was demonstrated by testing benzylpiperidine (2), which had almost no measurable activity in either assay.
为了研究强效致幻剂1-(1-苯基环己基)哌啶（PCP，1）中环烷基部分的结构要求，合成了一系列结构类似物，其中环烷基环的大小从三个碳原子变化到八个碳原子。这些化合物的生物活性通过体外试验（苯环己哌啶结合试验）和体内试验（辨别刺激试验）进行评估。随着环烷基环的大小从环己烷（PCP）的大小减小，两种试验中PCP样活性均下降，但当环烷基环的大小大于环己烷时，体内试验中观察到PCP样活性急剧下降，而体外试验中的活性仅略低于PCP。1-(1-苯基辛基)哌啶（8）在体外结合试验中具有强效竞争性结合特性，但在体内试验中未产生可观察到的PCP样效应。通过测试苄基哌啶（2）证明了环烷基环在PCP结构中的重要性，苄基哌啶在两种试验中几乎均无可测量的活性。
