C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors.
C1- and C3-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) have been synthesized, and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics (MMP2) calculations. The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (1S,2R)-7-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin [(+)-10] was demonstrated to be sevenfold less potent than (2R)-7-OH-DPAT as a DA receptor agonist. The other new compounds were of lower potency or inactive.
Johansson
A M
AM
Department of Organic Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Sweden.
Nilsson
J L
JL
Karlén
A
A
Hacksell
U
U
Sanchez
D
D
Svensson
K
K
Hjorth
S
S
Carlsson
A
A
Sundell
S
S
Kenne
L
L
D000818:Animals; D001058:Apomorphine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008958:Models, Molecular; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014961:X-Ray Diffraction
D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D001058:Apomorphine