Modulations of the amide function of the preferential dopamine D3 agonist (R,R)-S32504: improvements of affinity and selectivity for D3 versus D2 receptors.

Article Details

Citation

Peglion JL, Poitevin C, Mannoury La Cour C, Dupuis D, Millan MJ

Modulations of the amide function of the preferential dopamine D3 agonist (R,R)-S32504: improvements of affinity and selectivity for D3 versus D2 receptors.

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2133-8. doi: 10.1016/j.bmcl.2009.03.015. Epub 2009 Mar 9.

PubMed ID
19324548 [ View in PubMed
]
Abstract

Starting with the preferential dopamine (DA) D(3) agonist S32504, we prepared two series of derivatives of the general formula I-A and I-B, in an effort to improve both potency and selectivity. For the first set of derivatives, where the primary amide function of S32504 was replaced by either secondary and tertiary amide or ester, acid, nitrile and ketone, no improvement was obtained. Conversely, when the primary amide function was integrated in a lactam ring, an enhancement of affinity and selectivity was attained for the five-membered ring lactam but also for its five-membered ring lactone analogue.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
RopiniroleDopamine D2 receptorKi (nM)691.83N/AN/ADetails
RopiniroleDopamine D3 receptorKi (nM)36.31N/AN/ADetails