The (9-enantiomer of 5-fluoro-&hydroxy-2-(dipropylamino) tetralin [ (S)-2a; (S)-UH301] was the first reported 5-HTlA receptor antagonist. We now give a full account on the synthetic effort leading to the preparation of the racemate and the enantiomers of 2a. The crystal and molecular structure of 2a . HBr has been determined by X-ray diffraction and the absolute configuration has been deduced using statistical tests of the crystal!ographic R values. The unit cell is tetragonal (P4,2,2) with a = b = 13.2235(2), c = 39.560(1) A and contains two crystallographically independent molecules in each asymmetric unit. The two solid state conformers differ in the conformation of the N-propyl groups. The pharmacological characterization of the enantiomers was done by use of in vivo biochemical and behavioural assays in rats. The (R)-enantiomer of 2a is a 5-HTiA receptor agonist of low potency while (3-2a does not exhibit any agonist properties at 5-HTlA receptors. As a consequence of the opposing effects of the enantiomers, the racemate, rac-2a, does not produce any clear-cut effects in rats. The reduced efficacy of (S)-2a as compared to the well known 5HT1A receptor agonist t?-hydroxy-Z-(dipropy1amino)tetralin (1; 8-OH-DPAT) may be due to the fluoro-substituent induced negative potential of the aromatic ring.
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