R and S enantiomers of 11-hydroxy- and 10,11-dihydroxy-N-allylnoraporphine: synthesis and affinity for dopamine receptors in rat brain tissue.
The R-(-)- and S-(+)-enantiomers of 11-hydroxy-N-allyl (4), and 10,11-dihydroxy-N-allyl (3) congeners of 11-hydroxy-N-n-propylnorapomorphine (11-OH-NPa, 2) or N-n-propylnorapomorphine (NPA, 1) were synthesized. Binding affinity of these compounds at dopamine (DA) receptor sites was evaluated with a membrane preparation of corpus striatum from rat brain. The R/S enantiomeric receptor affinity ratio was enhanced by allylic substitution of 3 and 4 and their R isomers had high DA receptor affinity similar to that of the N-n-propyl congeners. These N-allylnoraporphines are proposed as useful precursors to the preparation of their tritiated N-n-propyl enantiomers.
Neumeyer
J L
JL
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston.
Gao
Y G
YG
Kula
N S
NS
Baldessarini
R J
RJ
D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D015259:Dopamine Agents / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001060:Aporphines; D015259:Dopamine Agents; D007202:Indicators and Reagents; D011954:Receptors, Dopamine; C067053:11-hydroxy-N-allylnoraporphine; C067052:10,11-dihydroxy-N-allylnoraporphine