Derivatives of 2-(dipropylamino)tetralin: effect of the C8-substituent on the interaction with 5-HT1A receptors
作者:Ye Liu、Hong Yu、Bjoern E. Svensson、Lourdes Cortizo、Tommy Lewander、Uli Hacksell
DOI:10.1021/jm00078a012
日期:1993.12
devoid of 5-HT1A receptor affinity, the compounds have moderate to high affinities (K(i) values range from 0.7 to 130 nM) for 5-HT1A receptors. Surprisingly, several of the derivatives do not produce any apparent effects in vivo although they have fairly high 5-HT1A receptor affinities. However, the methoxycarbonyl- and acetyl-substituted derivatives are potent 5-HT1A receptor agonists in vivo and exhibit
制备了一系列其中C8取代基不同的2-(二丙基氨基)四氢萘衍生物,并进行了药理学评价,以探讨C8取代基在基于2-氨基四氢萘的配体与血清素(5-HT1A)受体相互作用中的重要性。通过8-羟基-2-(二丙基氨基)四氢化萘(8-OH-DPAT,1)的对映异构体的三平面的钯催化反应制备对映纯衍生物。通过与[3H] -8-OH-DPAT在大鼠海马和皮层组织中的竞争实验,评估了化合物对5-HT1A受体的亲和力。另外,通过在大鼠中使用生化和行为测定,评估了化合物在体内对中心5-HT和多巴胺受体的刺激活性。除了没有5-HT1A受体亲和力的羧基取代的衍生物外,这些化合物对5-HT1A受体具有中等至高的亲和力(K(i)值在0.7到130 nM之间)。出乎意料的是,尽管几种衍生物具有相当高的5-HT1A受体亲和力,但它们在体内没有产生任何明显的作用。但是,甲氧基羰基和乙酰基取代的衍生物在体内是有效的5-HT1A受