JP6982358B1 - 金属糖質錯体 - Google Patents
金属糖質錯体 Download PDFInfo
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- JP6982358B1 JP6982358B1 JP2021538243A JP2021538243A JP6982358B1 JP 6982358 B1 JP6982358 B1 JP 6982358B1 JP 2021538243 A JP2021538243 A JP 2021538243A JP 2021538243 A JP2021538243 A JP 2021538243A JP 6982358 B1 JP6982358 B1 JP 6982358B1
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- 230000009401 metastasis Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 229940098466 sublingual tablet Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
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Abstract
Description
KSAc: チオ酢酸 S−カリウム
NaOMe: ナトリウムメトキシド
Et3PAuCl: クロロ(トリエチルホスフィン)金(I)
DMF: N,N−ジメチルホルミアミド
HOBt: 1−ヒドロキシベンゾトリアゾール
WSC HCl: 1−エチル−3−(3−ジメチルアミノプロピル)カルボジイミド塩酸塩
TMSOTf: トリフルオロメタンスルホン酸 トリメチルシリル
THF: テトラヒドロフラン
化合物3A(500mg,1.2mmol)から出発し、同様の方法で得た化合物Aと合わせて、無色アモルファスの化合物Aを1.7g(収率63%(2工程))得た。
化合物A50.7mgをメタノールに溶かし、5.00mLとした。セル長100mmのセルを用いて、比旋光度を10回測定し、最大値と最小値を外した平均値をとったところ、その平均値は+7.28度であった。
化合物B50.5mgをメタノールに溶かし、5.00mLとした。セル長100mmのセルで、20℃で、比旋光度を10回測定し、最大値と最小値を外した平均値をとったところ−8.73度であった。なお、既知のD体である化合物Aの比旋光度(+7.28度)と比較して、化合物BがL体であることが確認された。
化合物C101.2mgをメタノール10.0mLに溶かし、濃度1.01mg/mLのサンプル溶液を調製した。セル長100mmのセルを用いて、20℃で、比旋光度を10回測定し、最大値と最小値を外した平均値をとったところ+56.1度であった。なお、化合物CのD体であるオーラノフィンの比旋光度は−52度であり(Green Chemistry, 2015, 17, 4, 2545-2551参考)、化合物CがL体であることが確認できた。
実施例で得られた化合物について、以下に示す試験を行った。
本発明のL−グルコース誘導体による温度上昇効果を確認するために、図1に示すRF波照射ユニット10を用いて、ラジオ波(RF波)照射試験を行った。RF波照射ユニット10は、高周波発生器1と、高周波発生器1に接続された上部電極3及び下部電極5と、上部電極3と下部電極5との間で発生する電磁波を遮蔽するための電磁シールド7とを備える。上部電極3と下部電極5との間に試料Sを設置して、上部電極3と下部電極5の間で電磁波(RF波)を照射すると電気力線LEFが発生し、RF波照射試験を行うことができる。RF波照射の条件は、周波数(13.56MHz)とした。
マウスの膵β細胞の腫瘍化(インスリノーマ)細胞株MIN6(Miyazaki J. et al., Endocrinology 127: 126-132, 1990)を用いて、以下の実験を行なった。ここで、すべての実験は、96穴のウェルのなかに約1000個のMIN6細胞を前もって入れ、上記化合物B(以下LGGと呼ぶ)を投与する実験と、上記化合物A(以下DGGと呼ぶ)を投与する対照実験について、外的擾乱が極力ないように配慮して行なった。
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US5624908A (en) * | 1993-06-11 | 1997-04-29 | Valley Cancer Institute | Antineoplastic compositions |
JP2003113194A (ja) * | 2001-08-03 | 2003-04-18 | Fuji Photo Film Co Ltd | 新規金−硫黄化合物及び該化合物の合成法 |
WO2012133688A1 (ja) * | 2011-03-31 | 2012-10-04 | 国立大学法人弘前大学 | 蛍光標識されたl-グルコース誘導体を用いたがん細胞を検出するための方法及び該誘導体を含むがん細胞のイメージング剤 |
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US20080279781A1 (en) * | 2007-05-10 | 2008-11-13 | Brookhaven Science Associates, Llc | Glycosylated Carboranylporphyrins and Uses Thereof |
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US5624908A (en) * | 1993-06-11 | 1997-04-29 | Valley Cancer Institute | Antineoplastic compositions |
JP2003113194A (ja) * | 2001-08-03 | 2003-04-18 | Fuji Photo Film Co Ltd | 新規金−硫黄化合物及び該化合物の合成法 |
WO2012133688A1 (ja) * | 2011-03-31 | 2012-10-04 | 国立大学法人弘前大学 | 蛍光標識されたl-グルコース誘導体を用いたがん細胞を検出するための方法及び該誘導体を含むがん細胞のイメージング剤 |
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