916486-98-1Relevant articles and documents
trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: Synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist
Cueva, Juan Pablo,Giorgioni, Gianfabio,Grubbs, Russell A.,Chemel, Benjamin R.,Watts, Val J.,Nichols, David E.
, p. 6848 - 6857 (2007/10/03)
We report the synthesis of trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H- chromeno[3,4-c]isoquinoline hydrochloride 6 and the resolution of its enantiomers. This new compound is an oxygen bioisostere of the potent dopamine D1-selective full agonist dihydrexidine. The initial synthetic approach involved, as a key step, a Suzuki coupling between a chromene triflate and a boronate ester, followed by isoquinoline formation and reduction of the resulting isoquinoline. Subsequently, a more efficient route was developed that involved conjugate addition of an aryl Grignard reagent to a 2-nitrochromene. The title compound possessed high affinity (Ki = 20-30 nM) for porcine D1-like receptors in native striatal tissue and full intrinsic activity at cloned human dopamine D1 receptors but had much lower affinity at dopamine D2-like receptors (Ki = 3000 nM). The binding and functional properties of this compound illustrate again the utility of constructing dopamine D1 agonist ligands around the β-phenyldopamine pharmacophore template.
