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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis and dopamine antagonist activity of 2-thioether derivatives of the ergoline ring system
D E Tupper1, I A Pullar, J A Clemens
1Lilly Research Centre Ltd., Eli Lilly and Co., Windlesham, Surrey, U.K.
Abstract:
A series of 2-thioether derivatives of a number of clavine alkaloid (ergoline) ring systems have been synthesized and tested for dopamine antagonist activity. Of the compounds tested 2-(methylthio)-agroclavine (8,9-didehydro-6,8-dimethyl-2-(methylthio)ergoline) (6) was the most potent and had a profile of activity in animal models indicative of potential antipsychotic activity. The synthesis and biological activity of a number of metabolites of 6, including the 13-hydroxy derivative, are also reported.
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