(8.beta.)-Ergoline-8-carboxylic acid cycloalkyl esters as serotonin antagonists: structure-activity study

• Published in: Journal of medicinal chemistry 1988-02, Vol.31 (2), p.444-448
• Main Authors: Garbrecht, William L, Marzoni, Gifford, Whitten, Kathleen R, Cohen, Marlene L
• Format: Article
• Language: English
• Subjects: Animals; Chemistry; Ergolines - chemical synthesis; Ergolines - pharmacology; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Male; Organic chemistry; Preparations and properties; Rats; Rats, Inbred Strains; Receptors, Serotonin - drug effects; Serotonin Antagonists - chemical synthesis; Serotonin Antagonists - pharmacology; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00397a030

A series of (8 beta)-6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid cycloalkyl esters were prepared and examined for blockade of vascular 5HT2 receptors. The antagonist in this series that had the highest 5HT2 receptor affinity was (8 beta)-6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid cyclohexyl ester. This compound was therefore chosen as the basic backbone of a structure-activity study to determine what effect different N1-substituents, N6-substituents, and ester ring substituents had on 5HT2 receptor affinity. Maximal 5HT2 receptor affinity was obtained when the N1-substituent was isopropyl, the N6-substituent was methyl, and there was a hydroxy or keto substituent in the 4-position of the ester cyclohexyl ring.