Effect of 4-substitution on psychotomimetic activity of 2,5-dimethoxy amphetamines as studied by means of different substituent parameter scales.
Electron-withdrawing substituents at position 4 of 2,5-dimethoxy-substituted amphetamines increase, whereas electron-donating substituents decrease the psychotomimetic activity. The origin of this clearly localized effect is discussed. The uses of modified Hammett substituent scales (sigma(-) and sigma(+)), and especially the good sigma(+) correlation, strongly suggest that electron-donating substituents decrease the biological activity through a specific effect relating to the extent of the conjugative electron release from the 5-methoxy group to the phenyl ring.
Neuvonen
Kari
K
Department of Chemistry, University of Turku, FIN-20014 Turku, Finland. kari.neuvonen@utu.fi
Neuvonen
Helmi
H
Fülöp
Ferenc
F
D000662:Amphetamines / Q000737:chemistry*; D004583:Electrons; D006213:Hallucinogens / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000662:Amphetamines; D006213:Hallucinogens; D008024:Ligands; C036157:2,5-dimethoxyamphetamine