选择性多巴胺 D2 受体拮抗剂的合成与表征。2. L-741,626 的氮茚、苯并呋喃和苯并噻吩类似物。
Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626.
机构信息
Division of Radiological Sciences, Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO 63110, USA.
出版信息
Bioorg Med Chem. 2010 Jul 15;18(14):5291-300. doi: 10.1016/j.bmc.2010.05.052. Epub 2010 May 24.
Abstract
A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D2 versus D3 receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D2 binding affinity and the D2 versus D3 selectivity.
摘要
一系列吲哚、7-氮杂吲哚、苯并呋喃和苯并噻吩类化合物已经被合成并评估了它们与 D2 样多巴胺受体的亲和力。这些化合物与经典的 D2 样多巴胺受体拮抗剂氟哌啶醇、N-甲基哌啶酮和苯丙醇酮具有结构相似性。两个新化合物，4-(4-碘苯基)-1-((4-甲氧基-1H-吲哚-3-基)甲基)哌啶-4-醇（6）和 4-(4-碘苯基)-1-((5-甲氧基-1H-吲哚-3-基)甲基)哌啶-4-醇（7），被发现对 D2 受体具有高亲和力和选择性，而对 D3 受体则没有。将芳环系统从吲哚改变为其他杂芳环系统会降低 D2 结合亲和力和 D2 对 D3 的选择性。
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