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
- 巻
- 60
- 号
- 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
- ID情報
-
- DOI : 10.1021/acs.jmedchem.7b00817
- ISSN : 0022-2623
- eISSN : 1520-4804
- Web of Science ID : WOS:000408598500021