2-Haloaporphines as potent dopamine agonists.
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.
Ramsby
S
S
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
Neumeyer
J L
JL
Grigoriadis
D
D
Seeman
P
P
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D001060:Aporphines / Q000138:chemical synthesis* / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D015394:Molecular Structure; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D001060:Aporphines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C059951:2-fluoroapomorphine; D013134:Spiperone; D001058:Apomorphine