2-Aminotetralin-derived substituted benzamides with mixed dopamine D2, D3, and serotonin 5-HT1A receptor binding properties: A novel class of potential atypical antipsychotic agents
作者:Evert J. Homan、Swier Copinga、Lotta Elfström、Trees van der Veen、Jan-Pieter Hallema、Nina Mohell、Lena Unelius、Rolf Johansson、Håkan V. Wikström、Cor J. Grol
DOI:10.1016/s0968-0896(98)00167-9
日期:1998.11
class of potential atypical antipsychotic agents, based on the pharmacological concept of mixed dopamine D2 receptor antagonism and serotonin 5-HT1A receptor agonism, was designed by combining the structural features of the 2-(N,N-di-n-propylamino)tetralins (DPATs) and the 2-pyrrolidinylmethyl-derived substituted benzamides in a structural hybrid. Thus, a series of 35 differently substituted 2-aminotetralin-derived
通过结合2-(N,N-di-n-propylpropylamino)的结构特征,设计了一种新的化学类潜在的非典型抗精神病药,其基于混合的多巴胺D2受体拮抗作用和血清素5-HT1A受体激动作用的药理学概念结构杂化物中的四氢萘酮(DPAT)和2-吡咯烷基甲基衍生的取代苯甲酰胺。因此,合成了35种不同的2-氨基四氢萘衍生的取代的苯甲酰胺系列,并评估了这些化合物竞争与[3H]-雷氯必利与克隆的人多巴胺D2A和D3受体结合以及[3H] -8的竞争能力。 -OH-DPAT在体外与大鼠血清素5-HT1A受体结合。该系列的先导化合物5-甲氧基-2- [N-(2-苯甲酰胺基乙基)-Nn-丙基氨基]四氢化萘(12a)对多巴胺D2A受体表现出高亲和力(Ki = 3.2 nM),多巴胺D3受体(Ki = 0.58 nM)以及血清素5-HT1A受体(Ki = 0.82 nM)。该系列的结构亲和关系表明,在所有三种受