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    B ring reduced-D ring oxidized tetrapyrrolic photosensitizers for photodynamic therapy and tumor imaging
    1.
    发明授权
    B ring reduced-D ring oxidized tetrapyrrolic photosensitizers for photodynamic therapy and tumor imaging 有权
    B环还原-D环氧化四吡咯光敏剂用于光动力疗法和肿瘤成像

    公开(公告)号：US08679459B2

    公开(公告)日：2014-03-25

    申请号：US12918238

    申请日：2009-02-19

    申请人： Ravindra K. Pandey ,  Chao Liu ,  Mahabeer Dobhal ,  William Potter ,  Janet Morgan ,  Stephanie Pincus

    发明人： Ravindra K. Pandey ,  Chao Liu ,  Mahabeer Dobhal ,  William Potter ,  Janet Morgan ,  Allan Oseroff

    IPC分类号： A61B5/055 ,  C07B47/00 ,  C07D487/22

    CPC分类号： C07D487/22

    摘要： Tetrapyrrolic photosensitizers and imaging agent compounds having A, B, C, and D rings and having a reduced B ring and an oxidized D ring. The compounds preferably have a purity of at least 95 percent and preferably have a fused system connected at an unsaturated carbon atom of the C ring nearest the D ring and at the unsaturated carbon atom between the C and D rings. The invention also includes a method of making the compounds at over 95 percent yield by starting with a B and D ring oxidized tetrapyrollic compound and dissolving it in a halogenated hydrocarbon solvent and treating it with sufficient nitroalkane solution of FeCl36H2O to oxidize the D ring and separating the resulting organic layer and drying.

    摘要翻译： 具有A，B，C和D环的四吡咯类光敏剂和成像剂化合物，并具有还原的B环和氧化的D环。 化合物优选具有至少95％的纯度，并且优选具有在C环的最接近D环的不饱和碳原子和C和D环之间的不饱和碳原子连接的稠合体系。 本发明还包括通过用B和D环氧化的四元醇化合物开始制备化合物百分之九十五以上的方法，并将其溶解在卤代烃溶剂中，并用足够的FeCl 3·6H 2 O的硝基烷烃溶液处理以氧化D环并分离 所得有机层并干燥。

    B RING REDUCED-D RING OXIDIZED TETRAPYROLLIC PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY AND TUMOR IMAGING
    2.
    发明申请
    B RING REDUCED-D RING OXIDIZED TETRAPYROLLIC PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY AND TUMOR IMAGING 有权
    用于光化学治疗和肿瘤成像的B环减少D环氧化的光致变色光敏剂

    公开(公告)号：US20110264027A1

    公开(公告)日：2011-10-27

    申请号：US12918238

    申请日：2009-02-19

    申请人： Ravindra K. Pandey ,  Chao Liu ,  Mahabeer Dobhal ,  William Potter ,  Janet Morgan ,  Allan Oseroff ,  Stephanie Pincus

    发明人： Ravindra K. Pandey ,  Chao Liu ,  Mahabeer Dobhal ,  William Potter ,  Janet Morgan ,  Allan Oseroff ,  Stephanie Pincus

    IPC分类号： A61N5/00 ,  A61P35/00 ,  A61K51/04 ,  A61K49/00 ,  C07D487/22 ,  A61K49/04

    CPC分类号： C07D487/22

    摘要： Tetrapyrollic photosensitizers and imaging agent compounds having A, B, C, and D rings and having a reduced B ring and an oxidized D ring. The compounds preferably have a purity of at least 95 percent and preferably have a fused system connected at an unsaturated carbon atom of the C ring nearest the D ring and at the unsaturated carbon atom between the C and D rings. The invention also includes a method of making the compounds at over 95 percent yield by starting with a B and D ring oxidized tetrapyrollic compound and dissolving it in a halogenated hydrocarbon solvent and treating it with sufficient nitroalkane solution of FeCl3.6H2O to oxidize the D ring and separating the resulting organic layer and drying.

    摘要翻译： 具有A，B，C和D环并且具有还原的B环和氧化的D环的四味光敏剂和显影剂化合物。 化合物优选具有至少95％的纯度，并且优选具有在C环的最接近D环的不饱和碳原子和C和D环之间的不饱和碳原子连接的稠合体系。 本发明还包括一种通过用B和D环氧化的四羰基化合物开始制备化合物超过95％的方法，并将其溶解在卤代烃溶剂中并用足量的FeCl 3·6H 2 O的硝基烷烃溶液处理以氧化D环 并分离得到的有机层并干燥。

    Method for Enhancing Pdt Efficacy Using a Tyrosine Kinase Inhibitor
    4.
    发明申请
    Method for Enhancing Pdt Efficacy Using a Tyrosine Kinase Inhibitor 审中-公开
    使用酪氨酸激酶抑制剂提高Pdt功效的方法

    公开(公告)号：US20100256136A1

    公开(公告)日：2010-10-07

    申请号：US12309028

    申请日：2007-06-29

    申请人： Ravindra K. Pandey ,  Allan Oseroff ,  Stephanie Pincus ,  Janet Morgan ,  Xiang Zheng ,  Weiguo Liu

    发明人： Ravindra K. Pandey ,  Allan Oseroff ,  Stephanie Pincus ,  Janet Morgan ,  Xiang Zheng ,  Weiguo Liu

    IPC分类号： A61K31/5377 ,  A61K31/517 ,  A61K31/506 ,  A61K31/4045 ,  A61K31/409 ,  A61P35/00

    CPC分类号： A61K31/409 ,  A61K41/0061 ,  A61K41/0071

    摘要： A method for treating hyperproliferative tissue in a mammal which tissue expresses ABCG2 including the steps of: a) systemically introducing from about 100 to about 1000 mg/kg of body weight of a tyrosine kinase inhibiting compound into the mammal; b) within from about 0.5 to about 24 hours after the introducing in step a) systemically introducing from about 0.05 to about 0.5 μmol per kilogram of body weight of a tumor avid photosensitizing compound, that acts as a substrate for ABC family transport protein, ABCG2 and that has a preferential light absorbance frequency; and c) exposing the hyperproliferative tissue to light at a fluence of from about 50 to about 150 J/cm2 delivered at a rate of from about 5 to about 25 mW/cm2 at the light absorbance frequency. The photosensitizing compound is preferably a tetrapyrollic photosensitizer compound where the tetrapyrollic compound is a chlorin, bacteriochlorin, porphyrin, pheophorbide including pyropheophorbides, purpurinimide, or bacteriopurpurinimide and derivatives thereof; provided that, the photosensizing compound is not a meso-tetra (3-hydroxyphenyl) derivative, is not a saccharide derivative and is not a hematoporphyrin.

    摘要翻译： 一种用于治疗组织表达ABCG2的哺乳动物的过度增殖组织的方法，包括以下步骤：a）将约100至约1000mg / kg体重的酪氨酸激酶抑制化合物全身引入哺乳动物; b）在步骤a）中引入后约0.5至约24小时内，全身引入约0.05至约0.5μmol/千克体重的肿瘤avid光敏化合物，其作为ABC家族转运蛋白ABCG2的底物 并具有优先吸光度频率; 和c）以约5至约25mW / cm 2的速率在吸光度频率下以约50至约150J / cm 2的流量通量使过度增殖组织曝光。 光敏化合物优选为四级光敏剂化合物，其中四味化合物是二氢卟酚，细菌二氢卟酚，卟啉，含有偏高双歧杆菌，嘌呤酰亚胺或嘌呤嘌呤酰亚胺及其衍生物的脱镁叶绿素; 光敏化合物不是内消旋 - 四（3-羟基苯基）衍生物，不是糖衍生物，不是血卟啉。

    MULTIMODALITY AGENTS FOR TUMOR IMAGING AND THERAPY
    5.
    发明申请
    MULTIMODALITY AGENTS FOR TUMOR IMAGING AND THERAPY 审中-公开
    用于肿瘤成像和治疗的多功能剂

    公开(公告)号：US20110223102A1

    公开(公告)日：2011-09-15

    申请号：US12677381

    申请日：2008-09-11

    申请人： Ravindra K. Pandey ,  Suresh Pandey ,  Lalit Goswami ,  Allan Oseroff ,  Shipra Dubey ,  Munawwar Sajjad ,  Stephanie Pincus

    发明人： Ravindra K. Pandey ,  Suresh Pandey ,  Lalit Goswami ,  Allan Oseroff ,  Shipra Dubey ,  Munawwar Sajjad ,  Stephanie Pincus

    IPC分类号： A61K51/04 ,  A61K49/00 ,  A61K31/30 ,  A61K31/409 ,  A61K38/12 ,  A61K31/437 ,  A61K31/506 ,  A61P35/00 ,  A61P43/00

    CPC分类号： C07K7/06 ,  A61B5/02007 ,  A61B5/416 ,  A61K41/0071 ,  A61K47/54 ,  A61K47/64 ,  A61K49/0032 ,  A61K49/0036 ,  A61K49/0056 ,  A61K51/082 ,  A61K51/088

    摘要： A compound that is a conjugate of an antagonist to an integrin expressed by a tumor cell and at least one of a tumor avid tetrapyrollic photosensitizer, a fluorescent dye, and a radioisotope labeled moiety wherein the radioisotope is 11C, 18F, 64Cu, 124I, 99Tc, 111In or GdIII and its method of use for diagnosing, imaging and/or treating hyperproliferative tissue such as tumors. Preferably the photosensitizer is a tumor avid tetrapyrollic photosensitizer, e.g. a porphyrin, chlorin or bacteriochlorin, e.g. pheophorbides and pyropheophorbides. Such conjugates have extreme tumor avidity and can be used to inhibit or completely destroy the tumor by light absoption. The integrin is usually αvβ3, α5β1, αvβ5, α4β1, or α2β1. Preferably, the antagonist is an RGD peptide or another antagonist that may be synthetic such as a 4-{2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)ethyloxy}-benzoyl]amino-2-(S)-amino-ethyl-sulfonylamino group. Such compounds provide tumor avidity and imaging ability thus permitting selective and clear tumor imaging.

    摘要翻译： 作为拮抗剂与由肿瘤细胞表达的整联蛋白结合的化合物，以及至少一种肿瘤病毒四级光敏剂，荧光染料和放射性同位素标记部分，其中放射性同位素为11C，18F，64Cu，124I，99Tc ，111In或GdIII及其用于诊断，成像和/或治疗过度增生组织如肿瘤的方法。 优选地，光敏剂是肿瘤急性四分光敏光敏剂，例如。 卟啉，二氢卟酚或细菌二氢卟酚。 脱镁叶绿素和焦偏镁偏磷酸盐。 这种缀合物具有极端的肿瘤亲合力，可用于通过光吸收抑制或完全破坏肿瘤。 整合素通常为αv＆bgr; 3，α5和bgr; 1，αv＆bgr; 5，α4和bgr; 1或α2和bgr; 1。 优选地，拮抗剂是可以是合成的RGD肽或另一种拮抗剂，例如4- {2-（3,4,5,6-四 - 嘧啶-2-基氨基）乙氧基} - 苯甲酰基]氨基-2-（ S） - 氨基 - 乙基 - 磺酰基氨基。 这样的化合物提供了肿瘤亲合力和成像能力，从而允许选择性和清晰的肿瘤成像。

    Porphyrin-based compounds for tumor imaging and photodynamic therapy
    7.
    发明申请
    Porphyrin-based compounds for tumor imaging and photodynamic therapy 有权
    卟啉基化合物用于肿瘤成像和光动力学治疗

    公开(公告)号：US20100184970A1

    公开(公告)日：2010-07-22

    申请号：US12462535

    申请日：2009-08-05

    申请人： Ravindra K. Pandey ,  Munawwar Sajjad ,  Suresh Pandey ,  Amy Gryshuk ,  Allan Oseroff ,  Hani A. Nabi ,  Stephanie Pincus

    发明人： Ravindra K. Pandey ,  Munawwar Sajjad ,  Suresh Pandey ,  Amy Gryshuk ,  Allan Oseroff ,  Hani A. Nabi ,  Stephanie Pincus

    IPC分类号： C07D487/22

    CPC分类号： C07D487/22 ,  A61K51/0485 ,  C07H17/02

    摘要： This invention describes a first report on the synthesis of certain 124I-labelled photosensitizers related to chlorines and bacteriochlorins with long wavelength absorption in the range of 660-800 nm. In preliminary studies, these compounds show a great potential for tumor detection by positron emission tomography (PET) and treatment by photodynamic therapy (PDT). The development of tumor imaging or improved photodynamic therapy agent(s) itself represent an important step, but a dual function agent (PET imaging and PDT) provides the potential for diagnostic body scan followed by targeted therapy.

    摘要翻译： 本发明描述了关于在660-800nm范围内具有长波长吸收的氯和细菌二氢红素相关的某些124I标记的光敏剂的合成的第一报告。 在初步研究中，这些化合物通过正电子发射断层扫描（PET）和光动力学治疗（PDT）治疗显示出巨大的潜力。 肿瘤成像或改进的光动力治疗剂本身的发展本身就是重要的一步，但双重功能试剂（PET成像和PDT）提供诊断身体扫描的潜力，然后进行靶向治疗。

    Water soluble tetrapyrollic photosensitizers for photodynamic therapy
    8.
    发明授权
    Water soluble tetrapyrollic photosensitizers for photodynamic therapy 有权
    用于光动力疗法的水溶性四光镜光敏剂

    公开(公告)号：US07820143B2

    公开(公告)日：2010-10-26

    申请号：US12378751

    申请日：2009-02-19

    申请人： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    发明人： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    IPC分类号： A61B5/055

    CPC分类号： C07D471/22 ,  A61K41/0071 ,  A61K41/0076 ,  C09B47/00 ,  C09B69/108

    摘要： A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

    摘要翻译： 具有至少一个-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2或-N（CH 2 COOH）2基团的四酯类光敏剂化合物或其酯，所述四元醇化合物是二氢卟酚，细菌二氢卟酚，卟啉，焦脱镁叶绿素，嘌呤酰亚胺或细菌嘌呤酰亚胺。 理想地，化合物具有下式：或其药学上可接受的衍生物，其中R 1 -R 8和R 10是各种取代基，R 9是取代或未取代的-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2; 或-N（CH 2 COOH）2。 本发明还包括通过光注射化合物后用光处理的光动力学治疗方法和注射化合物后通过荧光成像的方法。

    WATER SOLUBLE TETRAPYROLLIC PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY
    9.
    发明申请
    WATER SOLUBLE TETRAPYROLLIC PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY 审中-公开
    水溶性光敏光敏剂光解动力疗法

    公开(公告)号：US20110091390A1

    公开(公告)日：2011-04-21

    申请号：US12912033

    申请日：2010-10-26

    申请人： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    发明人： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    IPC分类号： A61K49/00 ,  A61P35/00

    CPC分类号： C07D471/22 ,  A61K41/0071 ,  A61K41/0076 ,  C09B47/00 ,  C09B69/108

    摘要： A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1—R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

    摘要翻译： 具有至少一个-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2或-N（CH 2 COOH）2基团的四酯类光敏剂化合物或其酯，所述四元醇化合物是二氢卟酚，细菌二氢卟酚，卟啉，焦脱镁叶绿素，嘌呤酰亚胺或细菌嘌呤酰亚胺。 理想地，化合物具有下式：或其药学上可接受的衍生物，其中R 1 -R 8和R 10是各种取代基，R 9是取代或未取代的-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2; 或-N（CH 2 COOH）2。 本发明还包括通过光注射化合物后用光处理的光动力学治疗方法和注射化合物后通过荧光成像的方法。

    Water soluble tetrapyrollic photosensitizers for photodynamic therapy
    10.
    发明申请
    Water soluble tetrapyrollic photosensitizers for photodynamic therapy 有权
    用于光动力疗法的水溶性四光镜光敏剂

    公开(公告)号：US20090162289A1

    公开(公告)日：2009-06-25

    申请号：US12378751

    申请日：2009-02-19

    申请人： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    发明人： Ravindra K. Pandey ,  Amy Gryshuk ,  Lalit Goswami ,  William Potter ,  Allan Oseroff

    IPC分类号： A61K31/409 ,  A61P35/00 ,  A61K49/00 ,  A61K49/06

    CPC分类号： C07D471/22 ,  A61K41/0071 ,  A61K41/0076 ,  C09B47/00 ,  C09B69/108

    摘要： A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

    摘要翻译： 具有至少一个-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2或-N（CH 2 COOH）2基团的四酯类光敏剂化合物或其酯，所述四元醇化合物是二氢卟酚，细菌二氢卟酚，卟啉，焦脱镁叶绿素，嘌呤酰亚胺或细菌嘌呤酰亚胺。 理想地，化合物具有下式：或其药学上可接受的衍生物，其中R 1 -R 8和R 10是各种取代基，R 9是取代或未取代的-CH 2 CH 2 CON（CH 2 CON（CH 2 COOH）2）2; 或-N（CH 2 COOH）2。 本发明还包括通过光注射化合物后用光处理的光动力学治疗方法和注射化合物后通过荧光成像的方法。