脑显像剂二胺基二硫醇类化合物的合成  

SYNTHESIS OF DIAMINODITHIOL COMPLEXES AS NEW BRAIN IMAGING AGENTS

作　　者：严骏华[1] 陈兰福[1] 李德有[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药物化学杂志》1992年第4期1-9,共9页Chinese Journal of Medicinal Chemistry

摘　　要：为了寻找新型的脑显像剂,本文合成了六个二胺基二硫醇类化合物,这些化合物是由2,2′-二硫-二(2-甲基丙醛)和1,2-丙二胺(或乙二胺)缩合还原得到3,3,6,10,10-五甲基-1,2-二硫-5,8-二氮环癸烷,它与氯乙酰氯反应制得重要中间体5-氯乙酰基-3,3,6,10,10-五甲基-1,2-二硫-5,8-二氮环癸烷,用六氢吡啶取代该中问体中的氯得到5-(2′-哌啶基乙酰基)-3,3,6,10,10-五甲基-1,2-二硫-5,8-二氮环癸烷,此化合物先用四氢锂铝还原酰胺,然后再用氨基钠还原二硫键得到目的化合物2,2,6,9,9-五甲基-4,7-二氮-4-哌啶基乙基-1,10-癸二硫醇,包括中间体在内共合成了二十二个化合物,这些化合物均未见文献报道,它们的结构经元素分析,紫外,红外,质谱和核磁等光谱数据加以证实。利用配体交换法将这些化合物标记上了^(99m)Tc,标记率均达95％以上,初步的动物实验表明,在脑中有一定的摄取量,并有较长的停留时间。It was reported m this paper tb.at six diaminodithiol complexes were synthesized in order to find new brain imaging agents. The intermediate 3,3,6,10, 10-pentamethyl-1,2-dithia-5,8-diazacyclodeane(Ⅲ 1) was synthesized by condensation and reduction of 1,2-diaminopropane with 2,2′-dithia-bis(2-methylpropenel),which reacted with chloroacetylchloride to give the important intermediate 5- chloroacetyl-3,3,6,10,10-pentemethyl-1,2 dithia-5,8-diazacyclodeane (Ⅳ 1). The chloro-of (Ⅳ 1)was substituted with piperidinyl to give 5-(2′-pipreidinylacetyl)-3,3, 6, 10, 10-pentamethyl-1, 2-dithia-5, 8-diazacyclodeane (Ⅴ 1). 2,2,6,9,9-pentamethyl-4,7-diaza-4-pi-peridinyl-ethyl-1, 10-decanedithiol (Ⅷ) was synthesized to reduce (Ⅴ 1) with lithium aluminum and further with sodium in liquid ammonia. Twenty-two unreported compounds,including reaction intermediate were comfirmed by elemental and spectrum analyses. These compounds were labelled with Techtium-99m by the ligand exchange reaction. Their labelling percentages were>95％, the bisdistribution of these compounds in mice showed some uptake and longer retention.

关 键 词：合成 ^99mTc标记 2 2 6 9 9-五甲基-4 7-二氮-4-哌啶基乙基-1 10-癸二硫醇 二胺基二硫醇类化合物 

分 类 号：R914[医药卫生—药物化学]