Moriarty R M, Enache L A, Zhao L, Gilardi R, Mattson M V, Prakash O
Department of Chemistry, University of Illinois at Chicago 60607-7061, USA.
J Med Chem. 1998 Feb 12;41(4):468-77. doi: 10.1021/jm970059p.
Three phencyclidine (PCP) analogues possessing a highly rigid carbocyclic structure and an attached piperidine ring which is free to rotate were synthesized. Each analogue has a specific fixed orientation of the ammonium center of the piperidinium ring to the centrum of the phenyl ring. The binding affinities of the rigid analogues 1-piperidino-7,8-benzobicyclo[4.2.0]octene (14), 1-piperidinobenzobicyclo[2.2.1]heptene (16), and 1-piperidinobenzobicyclo[2.2.2]octene (13) for the PCP receptor ([3H]TCP) and th-receptor (NANM) were determined. The three analogues show low to no affinity for the PCP receptor but good affinity for the th-receptor and can be considered th-receptor selective ligands with PCP/th ratios of 13, 293, and 368, respectively. The binding affinities for the th-receptor are rationalized in terms of a model for the th-pharmacophore.
合成了三种具有高度刚性碳环结构且带有可自由旋转的哌啶环的苯环己哌啶（PCP）类似物。每个类似物的哌啶鎓环铵中心相对于苯环中心都有特定的固定取向。测定了刚性类似物1-哌啶基-7,8-苯并双环[4.2.0]辛烯（14）、1-哌啶基苯并双环[2.2.1]庚烯（16）和1-哌啶基苯并双环[2.2.2]辛烯（13）对PCP受体（[³H]TCP）和th受体（NANM）的结合亲和力。这三种类似物对PCP受体显示出低亲和力或无亲和力，但对th受体具有良好的亲和力，可被视为th受体选择性配体，其PCP/th比值分别为13、293和368。根据th药效团模型对th受体的结合亲和力进行了合理化解释。
