公开(公告)号：US20020022002A1

公开(公告)日：2002-02-21

申请号：US09891883

申请日：2001-06-26

申请人： The Regents of the University of California

发明人： Jorge R. Barrio ,  Andrej Petric ,  Nagichettiar Satyamurthy ,  Gary W. Small ,  Gregory M. Cole ,  Sung-Cheng Huang

IPC分类号： A61K051/00 ,  G01N033/48 ,  G01N001/30 ,  A61K031/519

CPC分类号： A61K51/0406 ,  A61K51/0455 ,  A61K51/0459

摘要： A method for labeling null-amyloid plaques and neurofibrillary tangles in vivo and in vitro, comprises contacting a compound of formula (I): 1 with mammalian tissue. In formula (I), R1 is selected from the group consisting of nullC(O)-alkyl, nullC(O)-alkylenyl-R4, nullC(O)O-alkyl, nullC(O)O-alkylenyl-R4, nullCnullC(CN)2-alkyl, nullCnullC(CN)2-alkylenyl-R4, 2 R4 is a radical selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl; R5 is a radical selected from the group consisting of nullNH2, nullOH, nullSH, nullNH-alkyl, nullNHR4, nullNH-alkylenyl-R4, nullO-alkyl, nullO-alkylenyl-R4, nullS-alkyl, and nullS-alkylenyl-R4; R6is a radical selected from the group consisting of nullCN, nullCOOH, nullC(O)O-alkyl, nullC(O)O-alkylenyl-R4, nullC(O)-alkyl, nullC(O)-alkylenyl-R4, nullC(O)-halogen, nullC(O)NH2, nullC(O)NH-alkyl, nullC(O)NH-alkylenyl-R4; R7 is a radical selected from the group consisting of O, NH, and S; and R8 is N, O or S. R2 and R3 are each independently selected from the group consisting of alkyl and alkylenyl-R10, wherein R10 is selected from the group consisting of nullOH, nullOTs, halogen, spiperone, spiperone ketal and spiperone-3-yl. Alternatively, R2 and R3 together form a heterocyclic ring, optionally substituted with at least one radical selected from the group consisting of alkyl, alkoxy, OH, OTs, halogen, alkylenyl-R10, carbonyl, spiperone, spiperone ketal and spiperone-3-yl. In the compounds of formula (I), one or more of the hydrogen, halogen or carbon atoms can, optionally, be replaced with a radiolabel.

摘要翻译： 一种用于在体内和体外标记β-淀粉样蛋白斑和神经原纤维缠结的方法，包括使式（I）化合物与哺乳动物组织接触。 在式（I）中，R 1选自-C（O） - 烷基，-C（O） - 亚烷基基-R 4，-C（O）O-烷基，-C（O）O-亚烷基 - R4，-C = C（CN）2-烷基，-C = C（CN）2 - 亚烷基-R4，R4为选自烷基，取代烷基，芳基和取代芳基的基团; R5是选自-NH2，-OH，-SH，-NH-烷基，-NHR4，-NH-亚烷基-R4，-O-烷基，-O-亚烷基-R4，-S-烷基的基团 和-S-亚烷基基-R4; R6是选自-CN，-COOH，-C（O）O-烷基，-C（O）O-亚烷基基-R4，-C（O） - 烷基，-C（O） - 亚烷基 -R 4，-C（O） - 卤素，-C（O）NH 2，-C（O）NH-烷基，-C（O）NH-亚烷基基-R4; R7是选自O，NH和S的基团; 并且R 8是N，O或S.R 2和R 3各自独立地选自烷基和亚烷基-R 10，其中R 10选自-OH，-OT，卤素，螺哌
酮，螺哌酮缩酮和螺哌隆 -3-基。 或者，R2和R3一起形成杂环，任选被至少一个选自烷基，烷氧基，OH，OT，卤素，亚烷基-R 10，羰基，螺哌
酮，螺哌酮缩酮和螺哌酮-3-基 。 在式（I）的化合物中，氢，卤素或碳原子中的一个或多个可以任选地被放射性标记代替。