The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors

Journal of Medicinal Chemistry
1985.0

Abstract

The pKa values for butaclamol (1), 1,2,3,5,6,10b beta-hexahydro-6 alpha-phenylpyrrolo[2,1-alpha]isoquinoline (2, McN-4612-Y), and 2-tert-butyl-1,3,4,6,7,11b beta-hexahydro-7 beta-phenyl-2H-benzo[alpha]quinolizin-2 alpha-ol (3, McN-4171) were determined to be 7.2, 9.1, and 7.0, respectively. The values for 1 and 3 are anomalous; however, the value for 1 (7.2) is not as low as the one reported in the literature (pKa = 5.9). We also determined pKa values for apomorphine, chlorpromazine, and lidocaine, for reference purposes (7.6, 9.2, and 7.9, respectively). The results indicate that 1 would not be predominantly unprotonated under the physiological conditions of receptor binding, rather it would be about 50% protonated. This fact may contravene a suggested binding model used to map the central dopamine receptor (viz., ref 3).

Knowledge Graph

Similar Paper

The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors
Journal of Medicinal Chemistry 1985.0
1,3-Diamino-6,7-dimethoxyisoquinoline derivatives as potential .alpha.1-adrenoceptor antagonists
Journal of Medicinal Chemistry 1988.0
Neuroleptics from the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 3. Carboxamidoalkyl derivatives
Journal of Medicinal Chemistry 1986.0
3-(4-Aminobutyn-1-yl)pyridines: binding at α4β2 nicotinic cholinergic receptors
Bioorganic & Medicinal Chemistry Letters 2004.0
Structural Investigation of the 7-Chloro-3-hydroxy-1H-quinazoline-2,4-dione Scaffold to Obtain AMPA and Kainate Receptor Selective Antagonists. Synthesis, Pharmacological, and Molecular Modeling Studies
Journal of Medicinal Chemistry 2006.0
Comparison of solution conformational preferences for the hallucinogens bufotenin and psilocin using 360-MHz proton NMR spectroscopy
Journal of Medicinal Chemistry 1981.0
6,7-Dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline. A structurally novel .beta.-adrenergic receptor blocking agent
Journal of Medicinal Chemistry 1986.0
N-Fluoroalkylated and N-alkylated analogs of the dopaminergic D-2 receptor antagonist raclopride
Journal of Medicinal Chemistry 1990.0
Synthesis of 2-(alkylamino)-5,6- and -6,7-dihydroxy-3,4-dihydroquinazolines and evaluation as potential dopamine agonists
Journal of Medicinal Chemistry 1982.0
1-(Aminomethyl)-6,7-dihydroxytetralin derivatives: synthesis and assessment of dopamine-like effects
Journal of Medicinal Chemistry 1983.0