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

ISSN:0018-019X
1983年第66卷第2期
Organische und biologische Chemie - Chimie organique et chimie biologique
Lucien Anker,Bernard Testa,Han Van De Waterbeemd,Anne Bornand-Crausaz,Andreas Theodorou,Peter Jenner,C. David Marsden

N-Aminoalkylbenzamides and 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 at the N-atom indicate the involvement of proximity and conformational effects. The complete inability of the compounds to displace 3H-spiperone and 3H-sulpiride from their specific rat striatal binding sites demonstrates the critical role of adequate aromatic substitution at positions 4 and 5.

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ISSN:0018-019X
1983年第66卷第2期
Organische und biologische Chemie - Chimie organique et chimie biologique

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