Synthesis, Pharmacological Investigation and Computational Studies on a Tricyclic Ergoline Analog with Selective Dopamine Autoreceptor Activity

Gmeiner P (1995)


Publication Type: Journal article

Publication year: 1995

Journal

Publisher: Wiley-VCH Verlag

Book Volume: 328

Pages Range: 609-614

DOI: 10.1002/ardp.19953280708

Abstract

The novel aminobenzindolone 8 was prepared and evaluated as a potential antipsychotic agent. The target compound was synthesized in eight steps starting from the tetrahydrobenzindolone 9. The key step of the synthesis was an electrophilic amination of the aromatic ketone 11 followed by reductive degradation when the diethoxymethyl group was employed for protection of the lactam nitrogen and also for the benzylic position 2a. Dopamine and serotonin receptor binding studies revealed 8 to be a potent and selective ligand at the D-2 autoreceptor (k(i) = 4.0 nM). Further in vivo studies including the GBL-test and locomotor activity measurements indicated agonistic activity of 8 at the prejunctional binding sites. Comparison of ab initio based molecular electrostatic isopotential maps corroborates our hypothesis that the dopamine structure 6, containing an intramolecular hydrogen bond donating effect of the meta-HO-group, represents the conformation which is active at the dopamine D-2 autoreceptor.

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How to cite

APA:

Gmeiner, P. (1995). Synthesis, Pharmacological Investigation and Computational Studies on a Tricyclic Ergoline Analog with Selective Dopamine Autoreceptor Activity. Archiv Der Pharmazie, 328, 609-614. https://doi.org/10.1002/ardp.19953280708

MLA:

Gmeiner, Peter. "Synthesis, Pharmacological Investigation and Computational Studies on a Tricyclic Ergoline Analog with Selective Dopamine Autoreceptor Activity." Archiv Der Pharmazie 328 (1995): 609-614.

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