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

Article abstract of DOI:10.1021/jm00164a029

A series of (8β)-6-methylergoline amide derivatives was synthesized with various alkyl substituents in the N¹-position in order to evaluate their effectiveness in blocking vascular 5HT₂ receptors. The influence of both the N¹ substituent and amide derivative proved to be of great importance on binding affinities to vascular 5HT₂ receptors. Within each series of amides, however, maximum affinity was achieved with an N¹-isopropyl substituent (14, 18, 26, 38, and 41; all with 2.7-5.0 times greater affinity than their N¹-H analogues), with the exception of two cases (22 and 37) in the cyclohexylamide derivatives wherein N¹-methyl equalled the isopropyl in potency. Other than these exceptions, affinities followed the pattern of H < Me < Et < iPr, with potencies falling off with larger alkyl substituents.