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    Photoactivatable compounds comprising benzochlorin and furocoumarin
    3.
    发明授权
    Photoactivatable compounds comprising benzochlorin and furocoumarin 失效
    包含苯并二氢卟酚和呋喃香豆素的可光活化化合物

    公开(公告)号：US6008211A

    公开(公告)日：1999-12-28

    申请号：US508238

    申请日：1995-07-27

    Applicant: Byron Robinson ,  Alan R. Morgan ,  Hugh L. Narciso, Jr.

    Inventor： Byron Robinson ,  Alan R. Morgan ,  Hugh L. Narciso, Jr.

    IPC: A61K31/366 ,  A61K31/407 ,  A61K31/409 ,  A61K31/4375 ,  A61K41/00 ,  A61P9/10 ,  A61P17/06 ,  A61P27/06 ,  A61P35/00 ,  C07D487/22 ,  C07D493/04 ,  C07D519/00 ,  A61K31/40

    CPC classification number: C07D493/04 ,  A61K41/0066 ,  A61K41/0071

    Abstract: A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.

    Abstract translation: 广泛的光敏化合物具有增强的体内靶组织选择性和光动力疗法的多功能性。 许多呋喃香豆素化合物，如补骨脂素，当光活化时表现出细胞抑制活性，但是在任何特定靶组织如动脉粥样硬化斑块中选择性积累，但体内特异性较小。 活性氧生产光敏剂（“ROPP”）是具有对过度增殖细胞（如动脉粥样硬化斑块细胞）的亲和力的光活化化合物，其在光活化时产生细胞毒性反应产物。 可以通过金属化卟啉来减少ROPP如卟啉的光活性，同时金属化ROPP对过度增殖组织的选择性亲和性基本上保持不变。 通过将呋喃香豆素化合物与ROPP连接以形成F-ROPP，可以利用F-ROPP的呋喃香豆素部分的细胞生长抑制性能，而化合物的ROPP部分对过度增殖细胞如动脉粥样硬化斑块的选择性亲和力提高 组织选择性没有细胞毒性。 在体内，某些F-ROPP可能被迫通过用具有可激活F-ROPP的F部分的光波长的光照射目标组织而选择性地累积在靶组织中，从而使F-ROPP形成单加合物 与目标组织中的细胞DNA交联或交联。 然后可以将第二波长的光递送到目标组织以激活ROPP部分，导致进一步干扰细胞活性。

    Chlorins processing fused ring systems useful as photoselective compounds for photodynamic therapy
    5.
    发明申请
    Chlorins processing fused ring systems useful as photoselective compounds for photodynamic therapy 有权
    用于光动力学治疗的紫杉烷加工稠环系统可用作光选择性化合物

    公开(公告)号：US20050020560A1

    公开(公告)日：2005-01-27

    申请号：US10922974

    申请日：2004-08-23

    Applicant: Byron Robinson ,  Dipanjan Sengupta ,  Avinash Phadke

    Inventor： Byron Robinson ,  Dipanjan Sengupta ,  Avinash Phadke

    IPC: A61K41/00 ,  C07D487/22 ,  A61K31/555

    CPC classification number: C07D487/22 ,  A61K41/0057 ,  A61K41/0071

    Abstract: The present invention provides a process of preparation of naphthochlorins and other chlorins with annelated ring systems useful for photodynamic therapy and the compounds themselves. The method for producing naphthochlorin compounds include contacting compounds such as meso-(2′-hydroxymethyl)phenyl porphyrin or meso-(2′-N,N,N-trialkylaminomethyl)phenyl porphyrin precursors with at least one acid catalyst at sufficient temperature for a sufficient time to yield the desired conversion. In a similar manner chlorins possessing annelated ring systems may be made from compounds such as meso-(2′-hydroxymethyl)aryl porphyrins or meso-(2′-N,N,N-trialkylaminomethyl)phenyl porphyrin. The procedures described herein provide new routes for synthesizing naphthochlorins and chlorins with annelated ring systems.

    Abstract translation: 本发明提供了用于光动力学治疗和化合物本身的具有环状环系的萘并氯和其他二氢卟酚的制备方法。 制造萘并二氢黄汞化合物的方法包括将内消旋 - （2'-羟甲基）苯基卟啉或中 - （2-N，N，N-三烷基氨基甲基）苯基卟啉前体的化合物与足够温度的至少一种酸催化剂接触， 足够的时间产生所需的转化。 类似地，具有环状环系的二氢卟酚可以由诸如中 - （2'-羟甲基）芳基卟啉或中 - （2-N，N，N-三烷基氨基甲基）苯基卟啉的化合物制备。 本文所述的方法提供用于合成具有环状环系的萘并氯和二氢卟酚的新途径。

    Compounds and method for PDT of intimal hyperplasia and other diseases
    6.
    发明授权
    Compounds and method for PDT of intimal hyperplasia and other diseases 失效
    PDT内膜增生等疾病的化合物和方法

    公开(公告)号：US06054449A

    公开(公告)日：2000-04-25

    申请号：US801829

    申请日：1997-02-14

    Applicant: Byron Robinson ,  Alan R. Morgan ,  Hugh L. Narciso, Jr.

    Inventor： Byron Robinson ,  Alan R. Morgan ,  Hugh L. Narciso, Jr.

    IPC: A61K31/366 ,  A61K31/407 ,  A61K31/409 ,  A61K31/4375 ,  A61K41/00 ,  A61P9/10 ,  A61P17/06 ,  A61P27/06 ,  A61P35/00 ,  C07D487/22 ,  C07D493/04 ,  C07D519/00 ,  A61K31/41 ,  C09B47/00 ,  C07D478/22

    CPC classification number: C07D493/04 ,  A61K41/0066 ,  A61K41/0071

    Abstract: A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.

    Abstract translation: 广泛的光敏化合物具有增强的体内靶组织选择性和光动力疗法的多功能性。 许多呋喃香豆素化合物，如补骨脂素，当光活化时表现出细胞抑制活性，但是在任何特定靶组织如动脉粥样硬化斑块中选择性积累，但体内特异性较小。 活性氧生产光敏剂（“ROPP”）是具有对过度增殖细胞（如动脉粥样硬化斑块细胞）的亲和力的光活化化合物，其在光活化时产生细胞毒性反应产物。 可以通过金属化卟啉来减少ROPP如卟啉的光活性，同时金属化ROPP对过度增殖组织的选择性亲和性基本上保持不变。 通过将呋喃香豆素化合物与ROPP连接以形成F-ROPP，可以利用F-ROPP的呋喃香豆素部分的细胞生长抑制性能，而化合物的ROPP部分对过度增殖细胞如动脉粥样硬化斑块的选择性亲和力提高 组织选择性没有细胞毒性。 在体内，某些F-ROPP可能被迫通过用具有可激活F-ROPP的F部分的光波长的光照射目标组织而选择性地累积在靶组织中，从而使F-ROPP形成单加合物 与目标组织中的细胞DNA交联或交联。 然后可以将第二波长的光递送到目标组织以激活ROPP部分，导致进一步干扰细胞活性。

    Efficient functionalization of porphyrin derivatives possessing sulfonic acid groups
    7.
    发明授权
    Efficient functionalization of porphyrin derivatives possessing sulfonic acid groups 失效
    具有磺酸基团的卟啉衍生物的高效官能化

    公开(公告)号：US5789586A

    公开(公告)日：1998-08-04

    申请号：US889114

    申请日：1997-07-07

    Applicant: Byron Robinson

    Inventor： Byron Robinson

    IPC: C07D487/22

    CPC classification number: C07D487/22

    Abstract: A method for preparing functionalized derivatives of organic or inorganic compounds and tetrapyrrolic compounds in particular, all of which compounds have at least one sulfonic acid group, by first preparing a sulfonyl halide intermediate of the compound then reacting the intermediate with a second compound having a reactive hydroxyl or amine group to yield the desired sulfonylamide or sulfonic esters thereof. The method may be used to produce a variety of photosensitive compounds having different functionality. For example, sulfonamide or sulfonic ester reaction products of the tetrapyrrolic compounds or other photosensitive organic molecules may exhibit an enhanced ability to localize at a particular target site for phototherapy. The method provides means for altering the functionality of sulfonic acid-containing photosensitive compounds to produce derivatives thereof which may aid in the detection and/or phototherapy of diseased sites or provide functionality having enhanced affinity and exhibiting improved binding to site specific receptors within a diseased target tissue such that the therapy is improved.

    Abstract translation: 通过首先制备化合物的磺酰卤中间体，然后使中间体与具有反应性的第二化合物反应，制备有机或无机化合物和四吡咯化合物的官能化衍生物的方法，特别是所有这些化合物具有至少一个磺酸基团 羟基或胺基，得到所需的磺酰胺或其磺酸酯。 该方法可用于生产具有不同功能的各种光敏化合物。 例如，四吡咯化合物或其它光敏有机分子的磺酰胺或磺酸酯反应产物可以表现出在特定靶位点定位以进行光疗的能力。 该方法提供了用于改变含磺酸的光敏化合物以产生其衍生物的功能的方法，其可以有助于病变部位的检测和/或光疗，或提供具有增强的亲和力并且显示改善的与病变靶内的位点特异性受体结合的功能 组织使得治疗得到改善。

    Photoactivatable compositions and to methods for the diagnosis and treating medical conditions
    8.
    发明授权
    Photoactivatable compositions and to methods for the diagnosis and treating medical conditions 失效
    与用于进行PDT的DNA形成和加合的组合物

    公开(公告)号：US5773609A

    公开(公告)日：1998-06-30

    申请号：US801831

    申请日：1997-02-14

    Applicant: Byron Robinson ,  Alan R. Morgan ,  Hugh L. Narciso, Jr.

    Inventor： Byron Robinson ,  Alan R. Morgan ,  Hugh L. Narciso, Jr.

    IPC: A61K31/366 ,  A61K31/407 ,  A61K31/409 ,  A61K31/4375 ,  A61K41/00 ,  A61P9/10 ,  A61P17/06 ,  A61P27/06 ,  A61P35/00 ,  C07D487/22 ,  C07D493/04 ,  C07D519/00 ,  A61K31/35

    CPC classification number: C07D493/04 ,  A61K41/0066 ,  A61K41/0071

    Abstract: A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.

    Abstract translation: 广泛的光敏化合物具有增强的体内靶组织选择性和光动力疗法的多功能性。 许多呋喃香豆素化合物，如补骨脂素，当光活化时表现出细胞抑制活性，但是在任何特定靶组织如动脉粥样硬化斑块中选择性积累，但体内特异性较小。 活性氧生产光敏剂（“ROPP”）是具有对过度增殖细胞（如动脉粥样硬化斑块细胞）的亲和力的光活化化合物，其在光活化时产生细胞毒性反应产物。 可以通过金属化卟啉来减少ROPP如卟啉的光活性，同时金属化ROPP对过度增殖组织的选择性亲和性基本上保持不变。 通过将呋喃香豆素化合物与ROPP连接以形成F-ROPP，可以利用F-ROPP的呋喃香豆素部分的细胞生长抑制性能，而化合物的ROPP部分对过度增殖细胞如动脉粥样硬化斑块的选择性亲和力提高 组织选择性没有细胞毒性。 在体内，某些F-ROPP可能被迫通过用具有可激活F-ROPP的F部分的光波长的光照射目标组织而选择性地累积在靶组织中，从而使F-ROPP形成单加合物 与目标组织中的细胞DNA交联或交联。 然后可以将第二波长的光递送到目标组织以激活ROPP部分，导致进一步干扰细胞活性。

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