(8 beta)-Ergoline-8-carboxylic acid cycloalkyl esters as serotonin antagonists: structure-activity study.
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.
Garbrecht
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Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Marzoni
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Whitten
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Cohen
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D000818:Animals; D004873:Ergolines / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists