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    SOLID PHASE SYNTHESIS OF ACRIDINIUM DERIVATIVES
    1.
    发明申请
    SOLID PHASE SYNTHESIS OF ACRIDINIUM DERIVATIVES 审中-公开
    茜素衍生物的固相合成

    公开(公告)号：US20090318627A1

    公开(公告)日：2009-12-24

    申请号：US12278621

    申请日：2007-02-06

    申请人： Anand Natrajan ,  David Sharpe ,  Jim Costello ,  Qingping Jiang

    发明人： Anand Natrajan ,  David Sharpe ,  Jim Costello ,  Qingping Jiang

    IPC分类号： C08G63/91 ,  C07D219/00 ,  C07J43/00 ,  C07K2/00 ,  C07H21/00

    CPC分类号： C07D219/04

    摘要： Acridinium-functionalized solid-phase supports and methods for making acridinium-functionalized solid-phase supports are disclosed. The acridinium-functionalized solid-phase supports comprise a solid phase support linked to a chemiluminescent substituted acridinium compound through a linker group covalently attached to the nitrogen atom of the acridinium nucleus and the solid phase support as exemplified in FIG. 1.

    摘要翻译： 公开了吖啶鎓官能化固相载体和制备吖啶酮官能化固相载体的方法。 吖啶酮官能化的固相载体包括通过共价连接到吖啶核的氮原子的连接基团和固相载体连接到化学发光的取代的吖啶鎓化合物的固相载体，如图1所示。 1。

    Near infrared chemiluminescent acridinium compounds and uses thereof
    3.
    发明授权
    Near infrared chemiluminescent acridinium compounds and uses thereof 有权
    近红外化学发光吖啶化合物及其用途

    公开(公告)号：US07611909B1

    公开(公告)日：2009-11-03

    申请号：US11266902

    申请日：2005-11-04

    申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

    发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

    IPC分类号： G01N33/533 ,  G01N21/76 ,  G01N33/53

    CPC分类号： G01N33/582 ,  C07D219/04 ,  Y10S436/80 ,  Y10S436/815 ,  Y10S436/817 ,  Y10S530/812 ,  Y10T436/13

    摘要： A method for the detection or quantitation of unlabeled target analyte in a biological sample, the method comprising labeling a target analyte for a biological sample suspected of containing unlabeled target analyte with an acridinium compound to form a labeled target analyte and providing the labeled target analyte to the biological sample, or providing the labeled target analyte to the biological sample, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus, with the electron-donating substituent attached at the C2 position. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (>590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

    摘要翻译： 一种用于检测或定量生物样品中未标记的靶分析物的方法，所述方法包括用怀疑含有未标记的靶分析物的生物样品用吖啶鎓化合物标记目标分析物以形成标记的目标分析物，并将标记的目标分析物 生物样品或将标记的靶分析物提供给生物样品，其中吖啶鎓化合物包含具有直接连接到吖啶核的给电子取代基的吖啶核，其中给电子取代基连接在C2位置。 可用于该方法的化学发光吖啶鎓化合物具有接近或在近红外（NIR）区域（> 590nm）中的发射最大值。 当与短波长发射的吖啶酯（发射最大值低于450nm）结合使用时，这些化学发光吖啶鎓化合物可以是在单次测定中同时检测多种靶分析物的非常有用的标记。

    Chemiluminescent Acridinium Compounds and Analogues thereof as Substrates of Hydrolytic Enzymes
    4.
    发明申请
    Chemiluminescent Acridinium Compounds and Analogues thereof as Substrates of Hydrolytic Enzymes 有权
    化学发光吖啶鎓化合物及其类似物作为水解酶的底物

    公开(公告)号：US20060202179A1

    公开(公告)日：2006-09-14

    申请号：US11422095

    申请日：2006-06-05

    申请人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

    发明人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

    IPC分类号： C09K3/00

    CPC分类号： C07D491/10 ,  C07D219/04 ,  C07F9/64 ,  C12Q1/42 ,  C12Q2334/00 ,  G01N33/533 ,  G01N33/582

    摘要： A chemiluminescent substrate of a hydrolytic enzyme having the following general Formula I is disclosed, as follows: Lumi-M-P   Formula I where “Lumi” is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached. Examples of Lumi include chemiluminescent acridinium compounds, benzacridinium compounds, quinolinium compounds, isoquinolinium compounds, phenanthridinium compounds, and lucigenin compounds, spiroacridan compounds, luminol compounds and isoluminol compounds. M is a multivalent heteroatom having at least one lone pair of electrons selected from oxygen, nitrogen and sulfur, directly attached to the light emitting moiety of Lumi at one end and to P at the other end. P is a group that can be readily removed by hydrolytic enzymes. An enzymatic reaction utilizing the above compound is the following: where HE is a hydrolytic enzyme. Lumi-M is a chemiluminescent product having physical and/or chemical properties different from those of Lumi-M-P.

    摘要翻译： 公开了具有以下通式I的水解酶的化学发光底物，如下所示：<？in-line-formula description =“In-line Formulas”end =“lead”？> Lumi-MP Formula I < line-formula description =“In-line Formulas”end =“tail”？>其中“Lumi”是能够自身产生光的化学发光部分（a），（b）MP附着和（c）附着M的化学发光部分。 Lumi的实例包括化学发光吖啶鎓化合物，苯并吖啶鎓化合物，喹啉鎓化合物，异喹啉鎓化合物，菲啶鎓化合物和光合精化合物，螺吡啶化合物，鲁米诺化合物和异鲁米诺化合物。 M是具有至少一个选自氧，氮和硫的孤对电子的多价杂原子，其一端直接连接到Lumi的发光部分，另一端直接附着于P。 P是可以通过水解酶容易地除去的基团。 使用上述化合物的酶反应如下：其中HE是水解酶。 Lumi-M是具有与Lumi-M-P不同的物理和/或化学性质的化学发光产物。

    Near infrared chemiluminescent acridinium compounds and uses thereof
    5.
    发明授权
    Near infrared chemiluminescent acridinium compounds and uses thereof 有权
    近红外化学发光吖啶化合物及其用途

    公开(公告)号：US07083986B2

    公开(公告)日：2006-08-01

    申请号：US10006421

    申请日：2001-12-06

    申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

    发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

    IPC分类号： G01N33/533 ,  G01N33/78 ,  G01N33/554 ,  G01N33/569 ,  C12Q1/68

    CPC分类号： G01N33/582 ,  C07D219/04 ,  Y10S436/80 ,  Y10S436/815 ,  Y10S436/817 ,  Y10S530/812 ,  Y10T436/13

    摘要： A method for the detection or quantitation of an analyte in a biological sample is disclosed. The method comprises the steps of selecting a biological sample suspected of containing a target analyte and binding the target analyte in the sample to a binding partner conjugated to an acridinium compound, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus at the C2 position. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (>590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

    摘要翻译： 公开了用于检测或定量生物样品中的分析物的方法。 该方法包括以下步骤：选择怀疑含有目标分析物并将样品中的目标分析物结合到与吖啶鎓化合物结合的结合对象的生物样品，其中所述吖啶鎓化合物包含具有直接连接的给电子取代基的吖啶核 到C> 2位上的吖啶核。 可用于该方法的化学发光吖啶鎓化合物具有接近或在近红外（NIR）区域（> 590nm）中的发射最大值。 当与短波长发射的吖啶酯（发射最大值低于450nm）结合使用时，这些化学发光吖啶鎓化合物可以是在单次测定中同时检测多种靶分析物的非常有用的标记。

    Measurement of hydride using chemiluminescent acridinium compounds and applications thereof
    10.
    发明授权
    Measurement of hydride using chemiluminescent acridinium compounds and applications thereof 有权
    使用化学发光吖啶化合物测量氢化物及其应用

    公开(公告)号：US06673560B1

    公开(公告)日：2004-01-06

    申请号：US09448522

    申请日：1999-11-23

    申请人： David Sharpe ,  Anand Natrajan ,  Qingping Jiang ,  George Parsons ,  Say-Jong Law

    发明人： David Sharpe ,  Anand Natrajan ,  Qingping Jiang ,  George Parsons ,  Say-Jong Law

    IPC分类号： G01N33536

    CPC分类号： G01N33/582 ,  C12Q1/008 ,  G01N33/581 ,  Y10S436/80 ,  Y10S436/815 ,  Y10T436/204165

    摘要： The present invention discloses a method for the measurement of hydride using a chemiluminescent compound. The preferred chemiluminescent molecule is an acridinium compound. The source of hydride for the reduction of acridinium compound may be of chemical or biochemical origin, or the result of enzymatic catalysis. The chemical source of hydride, for example, might be metal hydrides, such as NaBH4. A biochemical source of hydride might be that derived from NADH, or NADPH, while an enzymatic source would be the class of oxidoreductases termed dehydrogenases which convert NADH or NADPH from NAD or NADP. There are numerous potential applications for acridinium compounds as chemiluminescent indicators of hydride. Any applied tests or diagnostic assays, in which hydride is either present at the onset of or generated through the course of a reaction, would benefit from the present invention. Such tests, which could encompass many different formats as discussed below in detail, may involve the quantitation or detection of metal hydrides, or enzyme cofactors such as NADH, NADPH, FMNH2, or FADH2. Of particular importance, are those diagnostic assays which might use dehydrogenases as reagents, indicators, diagnostic markers or as labels. Ethanol, for example, might be detected with acridinium ester chemiluminescence through the reaction of alcohol dehydrogenase on ethanol, said reaction producing NADH. As a label, dehydrogenase might be used in an ELISA for the detection of a specific analyte with acridinium ester providing the signaling response. Nucleic acid assays using dehydrogenase as a label are also envisioned. Assays for the detection of clinically relevant dehydrogenases such as elevated glutamate dehydrogenase as an indicator of hepatocellular damage might also be developed.

    摘要翻译： 本发明公开了一种使用化学发光化合物测量氢化物的方法。 优选的化学发光分子是吖啶鎓化合物。 用于还原吖啶鎓化合物的氢化物源可以是化学或生物化学来源或酶催化的结果。 氢化物的化学源例如可以是金属氢化物，例如NaBH 4。 氢化物的生物化学来源可能是衍生自NADH或NADPH的酶，而酶源则是称为脱氢酶的氧化还原酶类，其从NAD或NADP转化NADH或NADPH。吖啶鎓化合物作为氢化物的化学发光指示剂有许多潜在应用 。 氢化物在反应过程中出现或产生的任何应用测试或诊断测定将从本发明中受益。 可以包括下面详细讨论的许多不同形式的这种测试可以涉及金属氢化物或酶辅因子如NADH，NADPH，FMNH 2或FADH 2的定量或检测。 特别重要的是那些可能使用脱氢酶作为试剂，指示剂，诊断标记物或标签的诊断测定法。 例如，乙醇可以通过醇脱氢酶对乙醇的反应用吖啶酯化学发光检测，所述反应产生NADH。 作为标记，脱氢酶可用于ELISA中，以检测具有吖啶酯的特异性分析物，从而提供信号反应。 也可以设想使用脱氢酶作为标记的核酸测定。 检测临床相关脱氢酶（如升高的谷氨酸脱氢酶作为肝细胞损伤指标）的检测也可能被开发出来。