Basicity, Lipophilicity, and Lack of Receptor Interaction ofN-Aminoalkylbenzamides andN-Aminoalkyl-o-anisamides as Model Compounds of Dopamine Antagonists
作者:Lucien Anker、Bernard Testa、Han Van De Waterbeemd、Anne Bornand-Crausaz、Andreas Theodorou、Peter Jenner、C. David Marsden
DOI:10.1002/hlca.19830660215
日期:1983.3.16
N-aminoalkyl-o-methoxybenzamides have been prepared and examined for their pKa, log P and dopamine receptor affinity. The pKa values range from ca. 7.5 for the derivatives having a one-C-atom side-chain, to ca. 10.3 for the N-aminobutyl derivatives. These variations with chain length are satisfactoryly explained by a field model. The variations in (log P)-values as a function of chain length and substitution
Ñ -Aminoalkylbenzamides和Ñ -aminoalkyl- ö -methoxybenzamides已经制备并检测它们的p ķ一个,登录P和多巴胺受体的亲和性。p K a值的范围从ca。对于具有一个-C原子侧链的衍生物,为约7.5 。10.3为N-氨基丁基衍生物。链长的这些变化可以通过现场模型得到令人满意的解释。(log P)值的变化作为链长和N原子取代的函数,表明存在邻近和构象效应。化合物完全不能取代来自其特定的大鼠纹状体结合位点的3 H-哌啶酮和3 H-磺胺必隆证明了在位置4和5进行足够的芳族取代的关键作用。