Abstract
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, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's 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 ([11C]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 11CO2 fixation after tin-lithium exchange at -20 °C afforded [11C]1. This methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of other compounds bearing π-rich heterocyclic rings. A PET/CT imaging study of [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 7139-7145 |
| Number of pages | 7 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 60 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Aug 24 2017 |
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ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
Synthesis of 11C-Labeled RXR Partial Agonist 1-[(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic Acid (CBt-PMN) by Direct [11C]Carbon Dioxide Fixation via Organolithiation of Trialkyltin Precursor and PET Imaging Thereof. / Shibahara, Osamu; Watanabe, Masaki; Yamada, Shoya; Akehi, Masaru; Sasaki, Takanori; Akahoshi, Akiya; Hanada, Takahisa; Hirano, Hiroyuki; Nakatani, Shunsuke; Nishioka, Hiromi; Takeuchi, Yasuo; Kakuta, Hiroki.
In: Journal of Medicinal Chemistry, Vol. 60, No. 16, 24.08.2017, p. 7139-7145.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Synthesis of 11C-Labeled RXR Partial Agonist 1-[(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic Acid (CBt-PMN) by Direct [11C]Carbon Dioxide Fixation via Organolithiation of Trialkyltin Precursor and PET Imaging Thereof
AU - Shibahara, Osamu
AU - Watanabe, Masaki
AU - Yamada, Shoya
AU - Akehi, Masaru
AU - Sasaki, Takanori
AU - Akahoshi, Akiya
AU - Hanada, Takahisa
AU - Hirano, Hiroyuki
AU - Nakatani, Shunsuke
AU - Nishioka, Hiromi
AU - Takeuchi, Yasuo
AU - Kakuta, Hiroki
PY - 2017/8/24
Y1 - 2017/8/24
N2 - 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, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's 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 ([11C]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 11CO2 fixation after tin-lithium exchange at -20 °C afforded [11C]1. This methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of other compounds bearing π-rich heterocyclic rings. A PET/CT imaging study of [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.
AB - 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, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's 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 ([11C]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 11CO2 fixation after tin-lithium exchange at -20 °C afforded [11C]1. This methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of other compounds bearing π-rich heterocyclic rings. A PET/CT imaging study of [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.
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U2 - 10.1021/acs.jmedchem.7b00817
DO - 10.1021/acs.jmedchem.7b00817
M3 - Article
C2 - 28753292
AN - SCOPUS:85028595602
VL - 60
SP - 7139
EP - 7145
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 16
ER -