2,5-Dimethoxy congeners of (+)-and (-)-3-(3-hydroxyphenyl)-N-n- propylpiperidine.
p-Dimethoxyaryl analogs of certain potent catechol-derived dopaminergic agonists show dopaminergic properties for which no structure-activity relationship has yet been defined. (S)-3-(3-Hydroxyphenyl)-N-n-propylpiperidine (1, S-"3-PPP") is a dopaminergic autoreceptor agonist, and at high doses it also exhibits postsynaptic antagonism. (R)-1 is a postsynaptic agonist. In a continuation of studies of effects of the p-dimethoxy moiety at dopamine receptors, synthesis and resolution of the 2,5-dimethoxy analog 3 of 3-PPP was undertaken. The two enantiomers and the racemic modification showed cardiovascular effects consistent with actions at DA-2 receptors. The potency of all three compounds was much lower than that of 3-PPP, although they displayed approximately the same duration of action. Absolute configuration does not seem to be a major determinant of these compounds' ability to interact with DA-2 receptors.
Cannon
J G
JG
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Kirschbaum
K S
KS
Amoo
V E
VE
Johnson
A K
AK
Long
J P
JP
D000818:Animals; D001919:Bradycardia / Q000139:chemically induced*; D015259:Dopamine Agents / Q000031:analogs & derivatives*; D007022:Hypotension / Q000139:chemically induced*; D010880:Piperidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D010880:Piperidines; C026539:preclamol