Lewis David, Zhang Ying, Prisinzano Thomas, Dersch Christina M, Rothman Richard B, Jacobson Arthur E, Rice Kenner C
Laboratory of Medicinal Chemistry, NIDDK, NIH, Bethesda, MD 20892, USA.
Bioorg Med Chem Lett. 2003 Apr 7;13(7):1385-9. doi: 10.1016/s0960-894x(03)00108-2.
A series of N-aromatic, N-heteroaromatic, and oxygenated N-phenylpropyl derivatives of 1-(2-benzhydryloxyethyl)-piperazine and 1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]piperazine, analogues of GBR 12909 (1a) and 12935 (1b), was synthesized and examined for their dopamine (DAT) and serotonin (SERT) transporter binding properties. One of these compounds, racemic 3-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-1-(3-fluorophenyl)-propan-1-ol (33), had DAT affinity as good as, or better than, GBR 12909 and 12935, and was more selective for DAT over SERT than the GBR compounds. Both trans- (43) and cis- (47) (+/-)-2-(4-[2-[bis-(4-fluorophenyl)-methoxy]ethyl]piperazin-1-ylmethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol had relatively good SERT selectivity and, as well, showed high affinity for SERT.
合成了一系列1-(2-二苯甲氧基乙基)哌嗪和1-[2-[双-(4-氟苯基)甲氧基]乙基]哌嗪的N-芳基、N-杂芳基和氧化N-苯基丙基衍生物，它们是GBR 12909(1a)和12935(1b)的类似物，并对其多巴胺(DAT)和5-羟色胺(SERT)转运体结合特性进行了研究。其中一种化合物，外消旋3-[4-(2-二苯甲氧基乙基)哌嗪-1-基]-1-(3-氟苯基)丙-1-醇(33)，其DAT亲和力与GBR 12909和12935相当或更好，并且相对于GBR化合物，其对DAT的选择性高于SERT。反式(43)和顺式(47)(±)-2-(4-[2-[双-(4-氟苯基)甲氧基]乙基]哌嗪-1-基甲基)-6-甲氧基-1,2,3,4-四氢萘-1-醇均具有相对较好的SERT选择性，并且对SERT也表现出高亲和力。
