甲氧基对苯酰胺类化合物受体亲合性的影响  

Effect of the Methoxy Group on the Affinity for the D2 Receptor with Benzamide Derivative

作　　者：胡欢[1] 盛许晶[1] 陈孟博[1] 朱建华[1] 

机构地区：[1]复旦大学药学院放射药学教研室,上海200032

出　　处：《复旦学报（医学版）》2005年第3期326-329,共4页Fudan University Journal of Medical Sciences

摘　　要：目的　研究甲氧基在苯酰胺类化合物与多巴胺D2受体(受体)结合中所起的作用。方法　合成(S) N [(1 乙基2 吡咯烷基)甲基] 4 氨基2 甲氧基苯甲酰胺(ABZM )的类似物(S) N [(1 乙基 2 吡咯烷基)甲基] 4 氨基 2 羟基苯甲酰胺(AHBZM)。用Iodogen法进行碘标记,反相高效液相色谱法(RP HPLC)鉴定、纯化得到标记物12 5I AIHBZM及12 5I AIBZM。通过体外受体放射配基结合分析和动物体内分布实验,比较上述两种标记物受体亲合力的大小。结果　成功制备了新化合物12 5I AIHBZM (放化纯度>99% )。测得AHBZM的IC50 值比ABZM的IC50 值大4～5个数量级。小鼠和大鼠的纹状体/小脑比值在0 .8～1.2。结论　甲氧基缺失后苯酰胺类化合物与受体特异结合的能力显著下降。Purpose To observe the effect of the meth ox y group on the affinity for the D2 dopamine receptor with benzamide derivatives. Methods (S)-N-[(1-ethyl-2-pyrrolidinyl)methy 1] -4-amine-2-hydro-xybenzamide (AHBZM), an analogue of (S)-N-[(1-ethyl-2 -pyrrolidinyl)methy 1]-4-amine-2-methoxybenzamide (ABZM),was synthesized.L abeling was achieved by the Iodogen method.Purifying was achieved by HPLC. 125 I-AIHBZM and 125I-AIBZM were prepared and compared their affinity for the D2 receptor by radioligand binding assay of receptors in vitro and biological distribution in rats and mice. Results 125I-AIHBZM was successfully prepare d,which had been purified by HPLC efficiently.The IC 50 value of AHBZM was larger than that of ABZM for nearly 1×105 times.The striatum/cerebellum ratio of 125I-AIHBZM was from 0.8 to 1.2. Conclusions Benzamide derivatives can not specially bin d with D2 receptor without the methoxy group.The methoxy group is an important f actor,which affects the affinity of Benzamide derivatives for the D2 receptor.

关 键 词：多巴胺D2受体 Iodogen 高效液相色谱法 放射配基分析 

分 类 号：R817.5[医药卫生—影像医学与核医学]