使用布他拉莫模板寻找副作用较小的抗精神病药物。
Use of the butaclamol template in a search for antipsychotic agents with lessened side effects.
作者信息
Kukla M J, Bloss J L, Brougham L R
出版信息
J Med Chem. 1979 Apr;22(4):401-6. doi: 10.1021/jm00190a009.
A number of molecular similarities between the antipsychotic agents butaclamol and clozapine were noted. Based on the premise that this was a strong indicator of a common mechanism of action (i.e., binding at the antagonist state of the dopamine receptor), a research approach was described. Three simplified analogues (4,8, and 12a) of butaclamol which still retained the molecular functionalities of the parent structure were synthesized and tested in the haloperidol receptor assay. 1-(5-Methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene)-4-tert-butyl-4-piperidine (12a) displaced tritiated haloperidol with an IC50 value of 2.4 nM, as compared to a value of 0.5 nM for butaclamol However, when 12a was tested in vivo or in the spiroperidol receptor assay it was found to be considerably less potent.
人们注意到抗精神病药物布他拉莫和氯氮平之间存在一些分子相似性。基于这是共同作用机制（即与多巴胺受体的拮抗剂状态结合）的有力指标这一前提，描述了一种研究方法。合成了布他拉莫的三种简化类似物（4、8和12a），它们仍保留母体结构的分子功能，并在氟哌啶醇受体测定中进行了测试。1-(5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯)-4-叔丁基-4-哌啶（12a）取代氚化氟哌啶醇的IC50值为2.4 nM，而布他拉莫的值为0.5 nM。然而，当在体内或螺哌啶醇受体测定中对12a进行测试时，发现其效力要低得多。
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