Perrone R, Berardi F, Colabufo N A, Leopoldo M, Tortorella V
Dipartimento Farmaco-Chimico, Universitá di Bari, via Orabona, 4, 70126 Bari, Italy.
J Med Chem. 1998 Nov 19;41(24):4903-9. doi: 10.1021/jm981041x.
A series of new 1-aryl-4-alkylpiperazines containing a terminal benzamide fragment or a tetralin-1-yl nucleus on the alkyl chain were synthesized and tested for binding at cloned human dopamine D4 and D2 receptor subtypes. A SAFIR (structure-affinity relationship) study on this series is herein discussed. The most relevant D4 receptor affinities were displayed by N-[omega-[4-arylpiperazin-1-yl]alkyl]-methoxybenzamides (compounds 5, 16-20), their IC50 values ranging between 0.057 and 7.8 nM. Among these, N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (17) emerged since it exhibited very high affinity for dopamine D4 receptor (IC50 = 0.057 nM) with selectivity of >10 000 for the D4 versus the D2 receptor; compound 17 was also selective versus serotonin 5-HT1A and adrenergic alpha1 receptors.
合成了一系列含有末端苯甲酰胺片段或烷基链上具有四氢萘-1-基核的新型1-芳基-4-烷基哌嗪，并测试了它们与克隆的人多巴胺D4和D2受体亚型的结合情况。本文讨论了该系列的结构-亲和力关系（SAFIR）研究。N-[ω-[4-芳基哌嗪-1-基]烷基]-甲氧基苯甲酰胺（化合物5、16 - 20）表现出最相关的D4受体亲和力，其IC50值在0.057至7.8 nM之间。其中，N-[2-[4-(4-氯苯基)哌嗪-1-基]乙基]-3-甲氧基苯甲酰胺（17）脱颖而出，因为它对多巴胺D4受体表现出非常高的亲和力（IC50 = 0.057 nM），对D4受体与D2受体的选择性大于10000；化合物17对5-羟色胺5-HT1A和肾上腺素α1受体也具有选择性。
