Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D(3) receptor-selective full agonist ligand.

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Clark AH, McCorvy JD, Conley JM, Williams WK, Bekkam M, Watts VJ, Nichols DE

Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D(3) receptor-selective full agonist ligand.

Bioorg Med Chem. 2012 Nov 1;20(21):6366-74. doi: 10.1016/j.bmc.2012.08.058. Epub 2012 Sep 8.

PubMed ID

23018094 [ View in PubMed

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Abstract

This work describes the identification of a novel class of octahydrobenzo[f]quinolines as dopamine D(3)-selective full agonists. We developed a facile method that utilizes Suzuki coupling for easy incorporations of various substituted pendant rings into the scaffold. A small focused library of octahydrobenzo[f]quinolines 5 was synthesized, and these compounds demonstrated at least 14-fold D(2)-like selectivity over D(1) in native porcine striatal tissue. Furthermore, n-propyl analog 5f was found to be a high affinity (K(i)=1.1 nM) D(3) dopamine full agonist with 145-fold selectivity over the D(2) receptor and about 840-fold selectivity over the D(1) receptor.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Chlorpromazine	Dopamine D2 receptor	Ki (nM)	1.2	N/A	N/A	Details
Chlorpromazine	Dopamine D3 receptor	Ki (nM)	3.8	N/A	N/A	Details