Document Report Card

ID: ALA1122468

Journal: J Med Chem

Title: Synthesis of (7R)-7H-indolo[3,4-gh][1,4]benzoxazines, a new class of D-heteroergolines with dopamine agonist activity.

Authors: Anderson PS, Baldwin JJ, McClure DE, Lundell GF, Jones JH, Randall WC, Martin GE, Williams M, Hirshfield JM, Clineschmidt BV, Lumma PK, Remy DC.

Abstract: Synthesis of several members of the 9-oxaergoline ring system is presented. Both the C/D cis and the C/D trans isomers of 4,6,6a,8,9,10a-hexahydro-7-ethyl-7H-indolo[3,4-gh] [1,4]benzoxazine were prepared, and the C/D trans isomer was resolved into its optical isomers. The enantiomer having the highest affinity for the [3H]apomorphine binding site, (-)-trans-6-ethyl-9-oxaergoline [(-)-6b], was shown to have the same absolute configuration as the natural ergolines, namely, 6aR, 10aR. In vivo and in vitro pharmacological evaluation shows these 9-oxaergolines to possess potent dopamine agonist properties.

CiteXplore: 6298427

DOI: 10.1021/jm00357a010