Tupper D E, Pullar I A, Clemens J A, Fairhurst J, Risius F C, Timms G H, Wedley S
Lilly Research Centre Ltd., Eli Lilly and Co., Windlesham, Surrey, U.K.
J Med Chem. 1993 Apr 2;36(7):912-8. doi: 10.1021/jm00059a017.
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.
已合成了一系列具有多种麦角灵生物碱（麦角oline）环系的2-硫醚衍生物，并对其多巴胺拮抗剂活性进行了测试。在所测试的化合物中，2-(甲硫基)-农麦角灵（8,9-二脱氢-6,8-二甲基-2-(甲硫基)麦角灵）（6）活性最强，在动物模型中的活性特征表明其具有潜在的抗精神病活性。还报道了6的多种代谢产物的合成及生物活性，包括13-羟基衍生物。
