TY - JOUR
T1 - Structural Requirements of Na+-Dependent Antidopaminergic Agents
T2 - Tropapride, Piquindone, Zetidoline, and Metoclopramide. Comparison with Na+-Independent Ligands
AU - Collin, Sonia
AU - Vercauteren, Daniel
AU - Vanderveken, Didier
AU - Evrard, Guy
AU - Durant, François
N1 - Publication code : **RES. ACAD.
PY - 1989
Y1 - 1989
N2 - Molecular graphic design coupled with PCILO and crystallographic results have been used to investigate the three-dimensional structure of Tropapride, Piquindone, Zetidoline, and Metoclopramide, four dopamine D-2 receptor antagonists showing Na+-dependent binding. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring and a carbonyl moiety, are similarly oriented in all the Na+-dependent drugs. Conversely, for Na+-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two Π-electron regions are systematically localized on the other side of the molecule: the first is a phenyl group while the second is a carbonyl function as in butyrophenones, a cyano group as in R48455, or a phenyl ring as in diphenylbutylpiperidines or tricyclics. The presence of a benzyl ring on this side in Tropapride might explain its weak extrapyramidal effects.
AB - Molecular graphic design coupled with PCILO and crystallographic results have been used to investigate the three-dimensional structure of Tropapride, Piquindone, Zetidoline, and Metoclopramide, four dopamine D-2 receptor antagonists showing Na+-dependent binding. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring and a carbonyl moiety, are similarly oriented in all the Na+-dependent drugs. Conversely, for Na+-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two Π-electron regions are systematically localized on the other side of the molecule: the first is a phenyl group while the second is a carbonyl function as in butyrophenones, a cyano group as in R48455, or a phenyl ring as in diphenylbutylpiperidines or tricyclics. The presence of a benzyl ring on this side in Tropapride might explain its weak extrapyramidal effects.
U2 - 10.1007/BF01590994
DO - 10.1007/BF01590994
M3 - Article
SN - 0920-654X
VL - 3
SP - 39
EP - 53
JO - Journal of computer-aided molecular design
JF - Journal of computer-aided molecular design
ER -