Division of Radiological Sciences, Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO 63110, USA.
Bioorg Med Chem. 2011 Jun 1;19(11):3502-11. doi: 10.1016/j.bmc.2011.04.021. Epub 2011 Apr 16.
A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D(₂-like) dopamine receptors. These compounds also share structural elements with the classical D(₂-like) dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D₂ receptor subtype with high affinity (K(i) values < 0.3 nM), (b) exhibit >50-fold D₂ versus D₃ receptor binding selectivity and (c) be partial agonists at both the D₂ and D₃ receptor subtype.
一系列与阿立哌唑（1）结构相关的化合物，阿立哌唑是一种临床用于治疗精神分裂症、双相情感障碍和抑郁症的非典型抗精神病药和抗抑郁药，已被制备并评估了它们对 D₂样多巴胺受体的亲和力。这些化合物还与经典的 D₂样多巴胺受体拮抗剂氟哌啶醇、N-甲基哌嗪酮、多潘立酮和苯海索具有结构元素。两种新化合物，7-(4-(4-(2-甲氧基苯基)哌嗪-1-基)丁氧基)-3,4-二氢喹啉-2(1H)-酮草酸盐（6）和 7-(4-(4-(2-(2-乙氧基)苯基)哌嗪-1-基)丁氧基)-3,4-二氢喹啉-2(1H)-酮草酸盐（7），（a）与 D₂受体亚型具有高亲和力（K(i)值<0.3 nM），（b）表现出对 D₃受体的>50 倍结合选择性，（c）在 D₂和 D₃受体亚型上均为部分激动剂。
