Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D(1) receptor activities.
Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D(1) receptor activities.
复制标题
DOI：
10.1016/j.bmc.2008.09.049
复制
发表时间：
2008-11
影响因子：
3.5
通讯作者：
Jing Zhang;Xuetao Chen;Leiping Yu;Xuechu Zhen;A. Zhang
中科院分区：
文献类型：
--
作者：
Jing Zhang;Xuetao Chen;Leiping Yu;Xuechu Zhen;A. Zhang
制备了一系列外消旋的6-芳基取代的1-苯基苯并氮杂卓7a-e和17 a、B。所有这些化合物对D1受体的结合效力均与原型（±）-SKF-38393（（±）-1）和（±）-SKF-83959（3）相容或远高于原型（±）-SKF-38393（（±）-1）和（±）-SKF-83959（3）。在（±）-SKF-38393的类似物中，化合物7 b、7 c和7 e分别具有10倍、2倍和7倍的D1受体结合增强。对于化合物7a和7 d，观察到比（±）-1更低但相容的效力。在（±）-SKF-83959（3）的骨架上引入了最佳的6位取代基（间甲苯基和2′-萘基）。所得化合物17 a、B对D1受体表现出高亲和力，仅略低于3。这两种化合物在D2受体上也显示出良好的结合。
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 D1receptor. Among analogs of (±)-SKF-38393, compounds 7b, 7c and 7e possess 10-, 2- and 7-fold enhancement in binding for the D1receptor, 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 D1receptor, only slightly lower than that of 3. These two compounds also showed good binding at the D2receptor.