論文 - 詳細
| RRC ID | 16019 |
|---|---|
| 著者 | Fujinaga M, Yamasaki T, Yui J, Hatori A, Xie L, Kawamura K, Asagawa C, Kumata K, Yoshida Y, Ogawa M, Nengaki N, Fukumura T, Zhang MR. |
| タイトル | Synthesis and evaluation of novel radioligands for positron emission tomography imaging of metabotropic glutamate receptor subtype 1 (mGluR1) in rodent brain. |
| ジャーナル | J Med Chem |
| Abstract |
We designed three novel positron emission tomography ligands, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-4-[(11)C]methoxy-N-methylbenzamide ([(11)C]6), 4-[(18)F]fluoroethoxy-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]7), and 4-[(18)F]fluoropropoxy-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]8), for imaging metabotropic glutamate receptor type 1 (mGluR1) in rodent brain. Unlabeled compound 6 was synthesized by benzoylation of 4-pyrimidinyl-2-methylaminothiazole 10, followed by reaction with isopropylamine. Removal of the methyl group in 6 gave phenol precursor 12 for radiosynthesis. Two fluoroalkoxy analogues 7 and 8 were prepared by reacting 12 with tosylates 13 and 14. Radioligands [(11)C]6, [(18)F]7, and [(18)F]8 were synthesized by O-[(11)C]methylation or [(18)F]fluoroalkylation of 12. Compound 6 showed high in vitro binding affinity for mGluR1, whereas 7 and 8 had weak affinity. Autoradiography using rat brain sections showed that [(11)C]6 binding is aligned with the reported distribution of mGluR1 with high specific binding in the cerebellum and thalamus. PET study with [(11)C]6 in rats showed high brain uptake and a similar distribution pattern to that in autoradiography, indicating the usefulness of [(11)C]6 for imaging brain mGluR1. |
| 巻・号 | 55(5) |
| ページ | 2342-52 |
| 公開日 | 2012-3-8 |
| DOI | 10.1021/jm201590g |
| PMID | 22316010 |
| MeSH | Animals Autoradiography Benzamides / chemical synthesis* Benzamides / chemistry Benzamides / pharmacokinetics Brain / diagnostic imaging* Brain / metabolism Fluorine Radioisotopes In Vitro Techniques Isotope Labeling Ligands Magnetic Resonance Imaging Male Mice Mice, Inbred C57BL Mice, Knockout Molecular Imaging Positron-Emission Tomography Radiopharmaceuticals / chemical synthesis* Radiopharmaceuticals / chemistry Radiopharmaceuticals / pharmacokinetics Rats Rats, Sprague-Dawley Receptors, Metabotropic Glutamate / genetics Receptors, Metabotropic Glutamate / metabolism* Structure-Activity Relationship Thiazoles / chemical synthesis* Thiazoles / chemistry Thiazoles / pharmacokinetics Tissue Distribution |
| IF | 6.205 |
| 引用数 | 30 |
| WOS 分野 | CHEMISTRY, MEDICINAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC01662 |