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

Journal of Medicinal Chemistry
1983.0

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.

Knowledge Graph

Similar Paper

Synthesis of (7R)-7H-indolo[3,4-gh][1,4]benzoxazines, a new class of D-heteroergolines with dopamine agonist activity
Journal of Medicinal Chemistry 1983.0
Synthesis of 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, a new class of dopamine agonists
Journal of Medicinal Chemistry 1984.0
Synthesis and dopaminergic activity of trans-6-methyl-7a,8,9,10,11,11a-hexahydro-7H-pyrrolo[3,2,1-gh]-4,7-phenanthroline and trans-1,2,3,4,4a,5,6,10b-octahydro-4,7-phenanthroline derivatives
Journal of Medicinal Chemistry 1986.0
Evaluation of cis- and trans-9- and 11-Hydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridines as Structurally Rigid, Selective D1 Dopamine Receptor Ligands
Journal of Medicinal Chemistry 1995.0
A series of hexahydro[1,4]oxazino[3,4-a]isoquinolines as potential neuroleptics
Journal of Medicinal Chemistry 1978.0
trans-2,3-Dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline:  Synthesis, Resolution, and Preliminary Pharmacological Characterization of a New Dopamine D<sub>1</sub>Receptor Full Agonist
Journal of Medicinal Chemistry 2006.0
Synthesis and dopaminergic activity of 2-substituted octahydrobenzo[f]quinolines
Journal of Medicinal Chemistry 1989.0
Centrally acting serotonergic and dopaminergic agents. 1. Synthesis and structure-activity relationships of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives
Journal of Medicinal Chemistry 1993.0
Synthesis, Resolution, and Preliminary Evaluation of trans-2-Amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and Related Derivatives as Dopamine Receptors Ligands
Journal of Medicinal Chemistry 1996.0
Facile synthesis of octahydrobenzo[h]isoquinolines: Novel and highly potent D1 dopamine agonists
Bioorganic &amp; Medicinal Chemistry 2010.0