Synthesis and Pharmacology of trans-4-n-Propyl-3,4,4a,10b-tetrahydro-2H,5H-1-benzopyrano-1,4-oxazin-7- and -9-ols: THe Significance of Nitrogen pKa Values for Central Dopamine Receptor Activation

Article abstract of DOI:10.1021/jm00119a020

The 6-oxa analogues of potent dopamine agonists, hexahydronaphthoxazines (4a, 4b), have been tested for dopamine receptor binding and stimulating activity and were found to be almost inactive. pK_a value determinations indicated that these compounds are protonated to ca. 2percent, while potent compounds are protonated to a much greater extent.These results strongly support the assumption that the protonated form of DA agonists is the active species at the receptor.