Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D(1) receptor activities.
A series of racemic 6-aryl substituted 1-phenylbenzazepines 7a-e, and 17a,b were prepared. All these compounds showed binding potencies compatible to or much higher than that of the prototypic (+/-)-SKF-38393 ((+/-)-1) and (+/-)-SKF-83959 (3) for the D(1) receptor. Among analogs of (+/-)-SKF-38393, compounds 7b, 7c and 7e possess 10-, 2- and 7-fold enhancement in binding for the D(1) receptor, respectively. Lower but compatible potency to that of (+/-)-1 was observed for compounds 7a and 7d. The optimal 6-substituents (m-tolyl, and 2'-naphthyl) were applied to the skeleton of (+/-)-SKF-83959 (3). The resulting compounds 17a,b displayed high affinity at the D(1) receptor, only slightly lower than that of 3. These two compounds also showed good binding at the D(2) receptor.
Zhang
Jing
J
Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Chen
Xuetao
X
Yu
Leiping
L
Zhen
Xuechu
X
Zhang
Ao
A
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D015394:Molecular Structure; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
C535181:3-methyl-1,6-di-(m-tolyl)-2,3,4,5-tetrahydro-1H benzo(d)azepine-7,8-diol; C535182:3-methyl-6-(naphthalen-2-yl)-1-m-tolyl-2,3,4,5-tetrahydro-1H-benzo(d)azepine-7,8-diol hydrobromide; D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959; D004298:Dopamine