論文

2017年8月

Synthesis of C-11-Labeled RXR Partial Agonist 14(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)aminoThenzotriazole-5-carboxylic Acid (CBt-PMN) by Direct [C-11]Carbon Dioxide Fixation via Organolithiation of Trialkyltin Precursor and PET Imaging Thereof

JOURNAL OF MEDICINAL CHEMISTRY
  • Osamu Shibahara
  • Masaki Watanabe
  • Shoya Yamada
  • Masaru Akehi
  • Takanori Sasaki
  • Akiya Akahoshi
  • Takahisa Hanada
  • Hiroyuki Hirano
  • Shunsuke Nakatani
  • Hiromi Nishioka
  • Yasuo Takeuchi
  • Hiroki Kakuta
  • 全て表示

60
16
開始ページ
7139
終了ページ
7145
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/acs.jmedchem.7b00817
出版者・発行元
AMER CHEMICAL SOC

The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, E-max = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimers and Parkinsons diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([C-11]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1. We found that (CO2)-C-11 fixation after tinlithium exchange at -20 degrees C afforded [C-11]1. This methodology may also be useful for synthesizing (CO2H)-C-11-PET tracer derivatives of other compounds bearing pi-rich heterocyclic rings. A PET/CT imaging study of [C-11]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.

リンク情報
DOI
https://doi.org/10.1021/acs.jmedchem.7b00817
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000408598500021&DestApp=WOS_CPL
ID情報
  • DOI : 10.1021/acs.jmedchem.7b00817
  • ISSN : 0022-2623
  • eISSN : 1520-4804
  • Web of Science ID : WOS:000408598500021

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