Dopaminergic activity and stereochemical considerations for rigid angular tricyclic congeners of dopamine: benzoquinoxalines and naphthothiazines.
Replacement of the oxygen atom at 1-position in the hexahydronaphthoxazines (4, PHNO) with a sulfur or nitrogen atom leads to the hexahydronaphthiazines (6, PHNT) and octahydro-benzoquinoxalines (5, POBQ) respectively and the 9-OH-PHNT shows to have a high affinity towards D-2 dopamine receptors in the binding assays; the racemic 9-OH-PHNT was then resolved and its absolute configuration was determined by CD. Inactivity on D-2 receptors of (+)-9-OCH3-PHNT 12 confirms the validity of the McDermed receptor model.
Perrone
R
R
Dipartimento Farmaco-Chimico, Università di Bari, Italy.
Berardi
F
F
Tortorella
V
V
Racagni
G
G
Rovescalli
A
A
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000138:chemical synthesis*; D011810:Quinoxalines / Q000138:chemical synthesis*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000494:pharmacology; D013237:Stereoisomerism; D013843:Thiazines / Q000138:chemical synthesis*
D001552:Benzazepines; D009281:Naphthalenes; D011810:Quinoxalines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013843:Thiazines; D013134:Spiperone; D004298:Dopamine