• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Ether-substituted isonitriles, Tc99m complexes thereof, and processes for myocardial tissue radioimaging using the Tc99m complexes.
    公开号:SU1635903A3
    申请号:SU894613202
    申请日:1989-01-09
    公开日:1991-03-15
    发明作者:Луис Бергстайн Пол；Субраманям Винаякам
    申请人:Е.И.Дюпон Де Немур Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of novel complex compounds.
    lower Tc of general formula
    ®ve
    (SY-A-DSS Gh6,
    where a means-C (CH3) ASND-,
    -CHN (CHB) y-, -CH (C%) or -C (CH3) / jai CHc-; X - inorganic anion, which can be used in medicine.
    The purpose of the invention is to find a method for producing new isonitrile 9 tTc complexes that are less absorbed by the liver and lungs and more easily removed from the liver at high absorption by the myocardium.
    The invention is illustrated by the following examples.
    Example 1. The following complex compounds are prepared:
    oe con
    with
    about with
    Complex A: / Wm Tc / C NC / CHs / o.CHftOCH, / 6 / Complex B: / EDt Tc / C NCH C / CHa / OCH, / + Complex C: / 99rn Tc / C NCH / CH / CH4OCH3 / 6 L Complex D: / "tts / С С / СНэ /, 2, СН2СН11ОСНз / 6 / Tert-Butylisonitrile complex (comparative
    Complex E: / WinTc / C NC / CH / 3/6 /

    about
    3-5 ml of isonitrile are dissolved in 1 ml of ethanol contained in a 10 cc serum vial. The vial is clogged. Then 100-150 tCnE9tpTs04, obtained by elution of a Mo / Tc radionuclide substance, are added. After that, 0.5 ml of a solution of 20-25 mg of sodium dithionite in 10 ml of distilled water is added, and the vial is placed for 15 min in a 100 C water bath. After cooling to room temperature, 1 ml of water is added, 1 ml of methylene chloride and extract the product with methylene chloride. The organic layer is evaporated, and the resulting product is dissolved in ethanol. The purity of the desired product is determined by thin layer chromatography on reverse phase plates of the Whatman C-18 type using as a solvent a mixture containing 22% 0.5 M aqueous ammonium acetate solution, 66% methanol, 9% acetonitrile and 3% THF, or a fast liquid chromatography on a reverse phase (5 mm) column of the Brownlee C-8 type using a mixture of 0.05 M aqueous solution of ammonium sulfate and methanol with a linear gradient in the range of 0-90% methanol as a solvent, within 20 min, and the delay after injection Ivanov is 1 min.
    Complex B is prepared analogously, but using 0.075 mg SnClg-H O and 1 mg L-cysteine hydrochloride as a reducing agent. The contents of the ampoule are boiled for 10 minutes and then cooled to room temperature. Complex B is obtained with a yield of more than 90%. Its purity is determined by reverse phase thin layer chromatography. (TLC R 0.40). The following TLC values were obtained for the Tc complexes of other ligands.
    ATLC R ligand {
    C (CH3) ČSN, 0.25
     0.45
     oh
    Example 2. The resulting complexes are evaluated by distributing them in individual guinea pig organs 5, 30 and 120 minutes after the injection. For each time interval, three guinea pigs are anaesthetized with sodium pentaprbitol (35 mg / kg intrabryugal), after
    0 o
    g with
    five
    He injected them with 0.1 ml of the test substance through the strap vein. The injected dose of the TTC-isonitrile is 1-2.5 tCi. After the guinea pigs are killed, individual organs are removed and their radioactivity is measured using a Capintec dose calibrator dosimeter or a gamma counter with a sample channel. The weight of the heart, lungs and liver is then measured. The results of measuring the distribution of radioactivity in the heart, lungs and liver for individual technetium complexes (99t) are given in the table.
    From the data on the ratio of the substance content in organs (hearts with the liver and hearts with the lungs), it can be seen that the described complexes have an advantage over the known structural analogue, which is expressed in their lower absorption by the lungs and liver and / or in their rather rapid leaching from the liver while maintaining high absorption of myocardial complexes, which allows them to be used with greater safety and efficacy for the diagnosis of myocardial infarction.
    权利要求:
    Claims (2)
    [1]
    Invention Formula
    qg y. A method for producing a TTC complex of general formula
    TctCN-A-OCHgVfx®,
    where A means - C (SNE) "
    [2]
    2.CHB-, -CH, gC (CH9) 2-, -CH (CH3) CHY- or -C (CH3), 3CH4CHe-j l- inorganic anion,
    characterized in that
    isonitrile formula
    CN-A-OCH3,
    where a has the specified value
    E9t gp-o ©
    interact with
    Tsol
    in the presence of sodium dithionite or a salt of divalent tin and cysteine.
    Priority featured:
    12/23/85 - obtaining compounds where A means - (, -CHftCtCHj) - or -CH () CH4-.
    11/06/86 for the preparation of the compound, where A represents -C (SP9) 2. (HCHCH -.
    Note All values are averages based on three animals.
     Calculated for each organ as a ratio of the% injected dose - per gram of tissue.
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    同族专利:
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE1215142C2|1964-07-09|1966-11-10|
    GB1187755A|1968-02-24|1970-04-15|Bayer Ag|A Process for the Production of Isonitriles|
    DE1962898A1|1969-12-16|1971-06-24|Bayer Ag|Process for the production of isonitriles|
    JPH0413348B2|1981-03-18|1992-03-09|Ici Plc|
    US4347251A|1981-07-13|1982-08-31|American Cyanamid Company|Novel 3-substituted amino-1-substituted heteroaryl-2-pyrazolines|
    US4452774A|1982-04-30|1984-06-05|President And Fellows Of Harvard College|Isonitrile radionuclide complexes for labelling and imaging agents|
    DE3343673A1|1983-12-02|1985-09-05|Basf Ag, 6700 Ludwigshafen|METHOD FOR THE SIMULTANEOUS PRODUCTION OF NITRILE AND ACRYLAMIDE OR METHACRYLAMIDE|
    US4707544A|1984-11-28|1987-11-17|President And Fellows Of Harvard College|Metal-isonitrile adducts for preparing radionuclide complexes for labelling and imaging agents|
    US4735793A|1985-08-30|1988-04-05|Massachusetts Institute Of Technology|Carboxy, carboalkoxy and carbamile substituted isonitrile radionuclide complexes|US5008418A|1987-09-11|1991-04-16|E. I. Du Pont De Nemours And Company|Triscopper adducts for preparing radionuclide complexes|
    US5028699A|1987-09-11|1991-07-02|E. I. Du Pont De Nemours And Company|Process for preparing Tc-99m tris copper complexes|
    US4885100A|1987-09-11|1989-12-05|E. I. Du Pont De Nemours And Company|Triscopper adducts for preparing radionuclide complexes|
    US4864051A|1988-09-02|1989-09-05|E. R. Squibb & Sons, Inc.|Process for preparing 2-methoxyisobutylisonitrile|
    WO1991019516A1|1990-06-18|1991-12-26|Mallinckrodt Medical, Inc.|Metal-radionuclide complex comprising isonitrile ligands|
    US5210270A|1991-11-25|1993-05-11|Institute Of Nuclear Energy Research|Method for synthesis and 99m C labelling of 2-alkoxyisobutylisonitrile|
    US5420321A|1993-08-03|1995-05-30|The Du Pont Merck Pharmaceutical Company|Triscopper sulfates for preparing radionuclide complexes|
    DE4445004A1|1994-12-16|1996-06-20|Consortium Elektrochem Ind|Composition for delocalized marking of objects, their manufacture and use|
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    US6416733B1|1996-10-07|2002-07-09|Bristol-Myers Squibb Pharma Company|Radiopharmaceuticals for imaging infection and inflammation|
    US20030124053A1|1996-10-07|2003-07-03|Barrett John Andrew|Radiopharmaceuticals for imaging infection and inflammation|
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    CN1136921C|2001-04-27|2004-02-04|北京师范大学|Myocardial developer and its prepn|
    MXPA04001113A|2001-08-08|2004-07-08|Bristol Myers Squibb Pharma Co|Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent.|
    US6838074B2|2001-08-08|2005-01-04|Bristol-Myers Squibb Company|Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent|
    US20050106100A1|2003-09-03|2005-05-19|Harris Thomas D.|Compounds containing matrix metalloproteinase substrates and methods of their use|
    WO2007005491A1|2005-06-30|2007-01-11|Bristol-Myers Squibb Pharma Company|Hydrazide conjugates as imaging agents|
    WO2007123934A2|2006-04-19|2007-11-01|The General Hospital Corporation|Aryl bidentate isonitriles and their uses|
    EP2099742A1|2006-10-30|2009-09-16|Draximage Limited|Methods for preparing 2-methoxyisobutylisonitrile and tetrakiscopper tetrafluoroborate|
    EP2821394A1|2013-07-01|2015-01-07|Fundacion MEDINA. Centro de Excelencia en Investigacion de Medicamentos Innovadores en Andalucia|Compounds with antibacterial activity|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US81247085A| true| 1985-12-23|1985-12-23|
    US92509186A| true| 1986-11-06|1986-11-06|
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