Basicity, Lipophilicity, and Lack of Receptor Interaction of N-Aminoalkylbenzamides and N-Aminoalkyl-o-anisamides as Model Compounds of Dopamine Antagonists

✍ Scribed by Lucien Anker; Bernard Testa; Han Van De Waterbeemd; Anne Bornand-Crausaz; Andreas Theodorou; Peter Jenner; C. David Marsden

• Book ID: 102858746
• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: German
• Weight: 731 KB
• Volume: 66
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19830660215

✦ Synopsis

Abstract

N‐Aminoalkylbenzamides and N‐aminoalkyl‐o‐methoxybenzamides have been prepared and examined for their p__K__~a~, log P and dopamine receptor affinity. The p__K__~a~ 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 at the N‐atom indicate the involvement of proximity and conformational effects. The complete inability of the compounds to displace ^3^H‐spiperone and ^3^H‐sulpiride from their specific rat striatal binding sites demonstrates the critical role of adequate aromatic substitution at positions 4 and 5.