(8 beta)-6-methylergoline amide derivatives as serotonin antagonists: N1-substituent effects on vascular 5HT2 receptor activity.

A series of (8β)-6-methylergoline amide derivatives was synthesized with various alkyl substituents in the N 1 -position in order to evaluate their effectiveness in blocking vascular 5HT 2 receptors. The influence of both the N 1 subsituent and amide derivative proved to be of great importance on binding affinities to vascular 5HT 2 receptors. Within each series of amides, however, maximum affinity was achieved with an N 1 -isopropyl substituent all with 2.7-50 times greater affinity than their N 1 -H analogues), with the exception of two cases in the cyclohexylamide derivatives wherein N 1 -methyl equalled the isopropyl in potency. Other than these exceptions, affinities followed the pattern of Hpotencies falling off with larger alkyl substituents