Scientific Article
previous document  unige:10675  next document
add to browser collection

Molecular electrostatic potential of orthopramides: implications for their interaction with the D-2 dopamine receptor

Van de Waterbeemd, Hans
Testa, Bernard
Published in Journal of Medicinal Chemistry. 1986, vol. 29, no. 5, p. 600-606
Abstract The electronic properties of orthopramides, a group of selective D-2 dopamine receptor antagonists, were investigated by calculating molecular electrostatic potentials (MEP) of model compounds with the ab initio STO-3G MO method. The various substitution patterns of the aromatic ring are characterized by a positive region comprising the H-bonded 2-methoxy group and ring positions 2, 3, and 4 and a negative region comprising the CONH group, 5-substituent, and ring positions 5 and 6. The regions of positive and negative potential are separated by a "curtain" running along the longitudinal axis of the molecule. At shorter distances from the plane of the aromatic ring (1.75 and 2.0 A), this "curtain" is quite sinuous, but at greater distances (2.5 and 3.0 A) it tends toward rectilinearity. We postulate that this longitudinal separation, together with the single positive maximum and the three negative minima perceptible at 3.0 A, constitute a distance pharmacophore responsible for the recognition and proper alignment of the ligand. The more complex MEP at 1.75 and 2.0 A are equated with a contact pharmacophore. Comparison of the MEP of orthopramides and dopamine reveals some analogies and suggests a possible mode of binding of these antagonists to the D-2 receptor.
Keywords Benzamides/*metabolismDopamine/metabolismElectrochemistryReceptors, Dopamine/*metabolism
Stable URL
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version:
PMID: 3701778

199 hits

0 download


Deposited on : 2010-08-06

Export document
Format :
Citation style :