ChemInform Abstract: Structure‐Activity Relationships in the 8‐Amino‐6,7,8,9‐tetrahydro‐3H‐ benz(e)indole Ring System. Part 1. Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes.

Abstract

Structure-Activity Relationships in the 8- 7,8,indole Ring System. Part 1. Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes.-A series of 1-and 4-substituted analogues such as (I) and (II), resp., (ca. 20 examples), and N-3-methylated derivatives of the potent 5-HTIA agonist (Ia) is prepared (in some cases in optically pure form). The analogues are investigated with respect to their in vitro binding activity to the serotonin 5-HT1A, 5-HT1Dα and 5-HT1Dβ and the dopamine D2 and D3 receptors, as well as to their in vivo agonist activity in reserpine-pretreated rats. All compounds are more or less selective for the 5-HT1A receptor. The substitution of the aldehyde group in (Ia) or (IIb) (equipotent to (Ia)) by other groups as shown in (Ib) to (If) decreases the affinity, while the introduction of the fluorine atom in the C-4 position does not change the pharmacological response. The affinity loss of N-methylated derivatives shows that the indole NH-moiety is crucial for drug-receptor interaction. -(STJERNLOEF, P.; ENNIS, M. D.; HANSSON, L. O.; HOFFMAN, R. L.; GHAZAL, N. B.; SUNDELL, S.; SMITH, M. W.; SVENSSON, K.; CARLSSON, A.; WIKSTROEM, H.; J. Med. Chem. 38 (1995) 12, 2202-2216; Dep. Pharm., Univ., S-413 90 Goeteborg, Swed.; EN) 1