公开(公告)号：US06306882B1

公开(公告)日：2001-10-23

申请号：US09424868

申请日：1999-12-08

申请人： Toshiaki Irie ,  Kiyoshi Fukushi ,  Hiroki Namba ,  Masaomi Iyo ,  Nobuo Ikota ,  Shinichiro Nagatsuka ,  Takao Ueda ,  Masaru Nishiura ,  Keizo Takatoku ,  Isamu Yomoda

发明人： Toshiaki Irie ,  Kiyoshi Fukushi ,  Hiroki Namba ,  Masaomi Iyo ,  Nobuo Ikota ,  Shinichiro Nagatsuka ,  Takao Ueda ,  Masaru Nishiura ,  Keizo Takatoku ,  Isamu Yomoda

IPC分类号： A61K31445

CPC分类号： C07D211/46 ,  A61K51/0455 ,  C07D211/42

摘要： The present invention relates to N-alkylpiperidine derivatives represented by general formula (1) or (2); wherein R1 represents optionally fluorinated lower alkyl; R2 represents lower alkyl; and R3 represents alkenyl substituted at the 1-position with hydroxy, lower alkoxy, lower alkoxyalkyloxy, lower alkoxyalkyloxyalkyloxy, or lower alkanoyloxy and substituted at the end with radioactive iodine, or alkenyloxymethyl substituted at the end with a radioactive iodine reagent containing the same for assaying central local AchE activity; a method for assaying the central local AchE activity; and labeled precursors of the above compounds. After easily passing through the blood-brain barrier, these compounds are hydrolyzed specifically by AchE in the brain into alcohols, which are then captured by the brain. In contrast, alcohols formed outside the brain do not migrate into the brain. The compounds of the invention emit &ggr;-rays at an appropriate energy level. These characteristics make the compounds highly useful as tracers for SPECT in assaying the central AchE activity.

摘要翻译： 本发明涉及由通式（1）或（2）表示的N-烷基哌啶衍生物，其中R 1表示任意氟化的低级烷基; R2代表低级烷基; R 3表示在1-位被羟基，低级烷氧基，低级烷氧基烷氧基，低级烷氧基烷氧基氧基或低级烷酰氧基取代的链烯基，末端用放射性碘取代，或末端用含有该取代基的放射性碘试剂取代的链烯氧基甲基 中央地方AchE活动; 测定中心局部AchE活性的方法; 和上述化合物的标记前体。 在容易通过血脑屏障之后，这些化合物被脑中的AchE特异性水解成醇，然后被脑捕获。 相比之下，形成在脑外的醇不会迁移到大脑中。 本发明的化合物以适当的能级发射γ射线。 这些特征使得化合物在测定中枢AchE活性时作为SPECT的示踪剂非常有用。

公开(公告)号：US20120107854A1

公开(公告)日：2012-05-03

申请号：US13255051

申请日：2009-03-03

申请人： Tatsuya Kikuchi ,  Toshiaki Irie ,  Kiyoshi Fukushi ,  Toshimitsu Okamura

发明人： Tatsuya Kikuchi ,  Toshiaki Irie ,  Kiyoshi Fukushi ,  Toshimitsu Okamura

IPC分类号： C12Q1/46 ,  C07D211/20

CPC分类号： C07D211/20 ,  C07D211/32 ,  C12Q1/46

摘要： An N-alkylpiperidine methanethiol ester derivative represented by any one of the general formulae (1) to (4) or a salt thereof has been discovered. The N-alkylpiperidine methanethiol ester derivative or the salt thereof has specificity for acetylcholinesterase or butyrylcholinesterase and is useful as a reagent for measurement of cholinesterase activity by the Ellman method.

摘要翻译： 已经发现了由通式（1）至（4）中的任一个表示的N-烷基哌啶甲硫醇酯衍生物或其盐。 N-烷基哌啶甲硫醇酯衍生物或其盐对乙酰胆碱酯酶或丁酰胆碱酯酶具有特异性，并且可用作通过Ellman方法测量胆碱酯酶活性的试剂。

公开(公告)号：US06509003B2

公开(公告)日：2003-01-21

申请号：US09764263

申请日：2001-01-19

申请人： Toshiaki Irie ,  Kiyoshi Fukushi ,  Hiroki Namba ,  Masaomi Iyo ,  Nobuo Ikota ,  Shinichiro Nagatsuka ,  Takao Ueda ,  Masaru Nishiura ,  Keizo Takatoku ,  Isamu Yomoda

发明人： Toshiaki Irie ,  Kiyoshi Fukushi ,  Hiroki Namba ,  Masaomi Iyo ,  Nobuo Ikota ,  Shinichiro Nagatsuka ,  Takao Ueda ,  Masaru Nishiura ,  Keizo Takatoku ,  Isamu Yomoda

IPC分类号： A61K5104

CPC分类号： C07D211/46 ,  A61K51/0455 ,  C07D211/42

摘要： The present invention relates to N-alkylpiperidine derivatives represented by general formula (1) or (2); wherein R1 represents optionally fluorinated lower alkyl; R2 represents lower alkyl; and R3 represents alkenyl substituted at the 1-position with hydroxy, lower alkoxy, lower alkoxyalkyloxy, lower alkoxyalkyloxyalkyloxy, or lower alkanoyloxy and substituted at the end with radioactive iodine, or alkenyloxymethyl substituted at the end with a radioactive iodine reagent containing the same for assaying central local AchE activity; a method for assaying the central local AchE activity; and labeled precursors of the above compounds. After easily passing through the blood-brain barrier, these compounds are hydrolyzed specifically by AchE in the brain into alcohols, which are then captured by the brain. In contrast, alcohols formed outside the brain do not migrate into the brain. The compounds of the invention emit &ggr;-rays at an appropriate energy level. These characteristics make the compounds highly useful as tracers for SPECT in assaying the central AchE activity.

摘要翻译： 本发明涉及由通式（1）或（2）表示的N-烷基哌啶衍生物，其中R 1表示任意氟化的低级烷基; R2代表低级烷基; R 3表示在1-位被羟基，低级烷氧基，低级烷氧基烷氧基，低级烷氧基烷氧基氧基或低级烷酰氧基取代的链烯基，末端用放射性碘取代，或末端用含有该取代基的放射性碘试剂取代的链烯氧基甲基 中央地方AchE活动; 测定中心局部AchE活性的方法; 和上述化合物的标记前体。 在容易通过血脑屏障之后，这些化合物被脑中的AchE特异性水解成醇，然后被脑捕获。 相比之下，形成在脑外的醇不会迁移到大脑中。 本发明的化合物以适当的能级发射γ射线。 这些特征使得化合物在测定中枢AchE活性时作为SPECT的示踪剂非常有用。