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 com...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1988-11, Vol.31 (11), p.2178-2182
Main Authors: Dijkstra, Durk, Mulder, Theo B. A, Rollema, Hans, Tepper, Pieter G, Van der Weide, Jan, Horn, Alan S
Format: Article
Language:English
Subjects:
Animals
Benzopyrans - chemical synthesis
Benzopyrans - pharmacology
Binding Sites - drug effects
Brain Chemistry
Cattle
Chemistry
Dopamine - metabolism
Dopamine Agents - chemical synthesis
Dopamine Agents - pharmacology
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Nitrogen - metabolism
Organic chemistry
Oxazines - chemical synthesis
Oxazines - pharmacology
Preparations and properties
Protons
Rats
Receptors, Dopamine - drug effects
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00119a020