Quantitative structure-activity relationships for substituted aminotetralin analogues. II: Inhibition of dopamine uptake

• Published in: Journal of pharmaceutical sciences Vol. 82; no. 5; p. 521
• Main Authors: Kim, K H, Basha, F, Hancock, A, DeBernardis, J F
• Format: Journal Article
• Language: English
• Published: United States 01.05.1993
• Subjects: Animals; Brain Chemistry - drug effects; Chemical Phenomena; Chemistry, Physical; Dopamine Antagonists; Lipids - chemistry; Male; Norepinephrine - metabolism; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Tetrahydronaphthalenes - chemistry; Tetrahydronaphthalenes - pharmacology
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600820518

Quantitative structure-activity relationships of 44 substituted aminotetralin analogues with regard to dopamine (DA) uptake inhibitory potency are examined in this study. Lipophilic substituents at R3 and hydrophilic substituents at R6 and/or R9 positions, as well as the overall lipophilicity of the molecule contribute toward increasing the inhibitory potency. Unlike with norepinephrine uptake inhibition, little effects are seen from the nitrogen substituent. Among the ring substituents examined, an hydroxy group at the R6 position increases the DA uptake inhibitory potency, whereas a methoxy group at the R7 position decreases it. A comparative quantitative structure-activity relationship study shows that a bromine at the R6 position and/or hydrogen at the R9 position make the compound a better norepinephrine uptake inhibitor than a DA uptake inhibitor, whereas hydrogen at the R6 and/or a substituent larger than a propyl group at the R2 position make the compound a more potent DA uptake inhibitor.