2-Aminotetralin-type compounds have long been shown to have a high affinity for the D2 family of dopamine receptors. The D2 family is now known to include D3 receptors, and recent results obtained with cloned dopamine receptors suggest that aminotetralin derivatives have preferential affinity for D3 as compared with D2 receptors. In our effort to develop selective ligands for the D3 receptor subtype, we explored the requirement in aminotetralins with dialkyl substitution on the amino moiety by changing one of the propyl group into a 2′-propynyl group and the other one into different alkyl-type substitutions. Our results demonstrated that the propyl group is not absolutely required as it can be replaced by the other groups without compromising its activity and selectivity. Furthermore, two of the new analogs in their racemic mixtures showed more selectivity than the (+)-enantiomer of 7-OH-DPAT in binding to the D3 receptor when assayed under the same conditions. Unlike 7-OH-DPAT, the most selective compound, (±)-6, exhibited no locomotor stimulation at the highest dose tested. Our study thus indicated that D3 receptor selective compounds might have opposite effects on locomotor action as compared with D2 receptor specific compounds.
|Original language||English (US)|
|Number of pages||22|
|Journal||Medicinal Chemistry Research|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Organic Chemistry