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

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Abstract
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 in rats. 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 (3). 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.