Synthesis and pharmacology of trans-4-n-propyl-3,4,4a,10b-tetrahydro-2H,5H-1-benzopyrano[4,3-b ]-1,4-oxazin-7- and -9-ols: the significance of nitrogen pKa values for central dopamine receptor activation.
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. pKa value determinations indicated that these compounds are protonated to approximately 2%, 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.
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001923:Brain Chemistry; D002417:Cattle; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D009584:Nitrogen / Q000378:metabolism*; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011522:Protons; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects
D001578:Benzopyrans; D015259:Dopamine Agents; D010078:Oxazines; D011522:Protons; D011954:Receptors, Dopamine; D009584:Nitrogen; D004298:Dopamine