Ergot alkaloids. Synthesis of 6-methyl-8-ergolenes as inhibitors of prolactin release.
A general synthetic route from elymoclavine (4a) to a variety of C-17 substituted 8-ergolenes has been established. [The C-17 position is the carbon attached to C-8 of the ergoline (1) skeleton as indicated in structure 2.] This route involves displacement reactions on the allylic chloride (4h) prepared from 4a by reaction with thionyl chloride. Conversion of the naturally occurring tricyclic clavines, chanoclavine I (5a) and isochanoclavine I (5b), to the tetracyclic clavine, agroclavine (4i), has been achieved. The new compounds prepared were tested for prolactin-inhibiting ability and were found to possess activity. One of the compounds prepared, 6-methyl-8-ergolenylacetamide (4k), was very potent, comparing favorably in activity to the best prolactin inhibitors reported to date.
D000818:Animals; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000097:blood; D051381:Rats; D013329:Structure-Activity Relationship
D004873:Ergolines; D011388:Prolactin