C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors

A M Johansson; J L Nilsson; A Karlén; U Hacksell; D Sanchez; K Svensson; S Hjorth; A Carlsson; S Sundell; L Kenne

doi:10.1021/jm00393a025

C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors

J Med Chem. 1987 Oct;30(10):1827-37. doi: 10.1021/jm00393a025.

Authors

A M Johansson¹, J L Nilsson, A Karlén, U Hacksell, D Sanchez, K Svensson, S Hjorth, A Carlsson, S Sundell, L Kenne

Affiliation

¹ Department of Organic Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Sweden.

PMID: 3656358
DOI: 10.1021/jm00393a025

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apomorphine / metabolism
Magnetic Resonance Spectroscopy
Methylation
Models, Molecular
Motor Activity / drug effects
Naphthalenes / pharmacology*
Rats
Receptors, Dopamine / metabolism*
Structure-Activity Relationship
Tetrahydronaphthalenes / pharmacology*
X-Ray Diffraction

Substances

Naphthalenes
Receptors, Dopamine
Tetrahydronaphthalenes
Apomorphine