2-Haloaporphines as potent dopamine agonists

• Published in: Journal of medicinal chemistry Vol. 32; no. 6; pp. 1198 - 1201
• Main Authors: Ramsby, Sten, Neumeyer, John L, Grigoriadis, Dimitri, Seeman, Philip
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-06-1989
• Subjects: Animals; Apomorphine - analogs & derivatives; Apomorphine - chemical synthesis; Apomorphine - metabolism; Aporphines - chemical synthesis; Aporphines - metabolism; Chemical Phenomena; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Molecular Structure; Organic chemistry; Pituitary Gland, Anterior - metabolism; Preparations and properties; Receptors, Dopamine - metabolism; Receptors, Dopamine D2; Spiperone - metabolism; Structure-Activity Relationship; Swine; Sympathomimetic
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00126a009

The synthesis of 2-amino- and 2-halo-substituted aporphines is described. The key step is the substitution of a hydroxy group in the 2-position with an amino group effected by a Smiles rearrangement reaction of the 2-methylpropanamide derivative 6. The affinity of the new compounds for the dopamine D-2 receptor in the anterior pituitary gland was evaluated. 2-Fluoroapomorphine was the most potent compound, being 1.5 times more potent than (-)-apomorphine. The structure-activity relationships are discussed in relation to a previously proposed receptor model.