ChemInform Abstract: Structure‐Activity Relationships in the 8‐Amino‐6,7,8,9‐tetrahydro‐3H‐ benz(e)indole Ring System. Part 2. Effect of 8‐Amino Nitrogen Substitution on Serotonin Receptor Binding and Pharmacology.

Abstract

Structure-Activity Relationships in the 8- 7,8,indole Ring System. Part 2. Effect of 8-Amino Nitrogen Substitution on Serotonin Receptor Binding and Pharmacology.-In continuation of the preceding paper a series of nonformylated (I) and formylated analogues (II) (ca. 30 examples) of the potent and selective agonist (IIa) is prepared in which the dipropylamino group is modified. The substituent influence of these compounds (as racemic mixtures or in some cases in optically pure form) on the in vitro receptor binding with respect to the 5-HT1A, 5-HT1Dα, 5-HT1D. beta., and dopamine D2 and D3 sites as well as their in vivo pharmacology in reserpinized rats is investigated. Nearly all of these analogues exhibit excellent activity for the 5-HT1A receptor and good selectivity for serotonine over dopamine sites. Generally, the (R)-enantiomers possess the superior receptor affinity, and those analogues having a good affinity for 5-HT1A also show clear agonist pharmacology. -(ENNIS, M. D.; STJERNLOEF, P.; HOFFMAN, R. L.; GHAZAL, N. B.; SMITH, M. W.; SVENSSON, K.; WIKSTROEM, H.; HAADSMA-SVENSSON, S. R.; LIN, C.-H.; J.