Monomethyl ether derivatives of 7,8-dihydroxy- and 8,9-dihydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines as possible products of metabolism by catechol-O-methyltransferase.
In order to facilitate identification of possible metabolites arising from in vitro action of catechol-O-methyltransferase upon 7,8-dihydroxy- and 8,9-dihydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines (11, 12), all four possible monomethyl ether derivatives have been synthesized. Incubation of 11 and 12 with the enzyme revealed that the 8,9-dihydroxy positional isomer 12 (which contains the dopamine moiety held in the beta conformation) but not the 7,8-dihydroxy isomer 11 (which holds the dopamine moiety in the alpha conformation) was a substrate for the enzyme. The sole detectable product of 12 was 8-hydroxy-9-methoxy derivative 15 in which the "meta" hydroxy group of the dopamine moiety is etherified.
Cannon
J G
JG
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Walker
K A
KA
Montanari
A
A
Long
J P
JP
Flynn
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002415:Cats; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D015394:Molecular Structure; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D006912:Hydroxyquinolines; D007202:Indicators and Reagents; D002394:Catechol O-Methyltransferase