(+/-)-3-Allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepin, a new high-affinity D1 dopamine receptor ligand: synthesis and structure-activity relationship.
The 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines form a series of compounds having a high affinity at the D1 dopamine receptor. The 6-chloro derivative has been previously shown to have enhanced affinity, selectivity, and agonist activity. In an attempt to study the effect of substitution of a 6-bromo group in place of the 6-chloro, we have synthesized a series of compounds and evaluated them for their affinity for the D1 receptor. The results show that the 6-bromo derivatives have virtually identical affinities to their 6-chloro counterparts, a finding similar to that found in the D1 antagonist 7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine series. From the present work, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepi ne (6-Br-APB) has been identified as a suitable candidate for further in vivo studies and resolution into its active and inactive enantiomers.
Neumeyer
J L
JL
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
Baindur
N
N
Niznik
H B
HB
Guan
H C
HC
Seeman
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004285:Dogs; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D008024:Ligands; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C074280:3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine