公开(公告)号：US07078014B2

公开(公告)日：2006-07-18

申请号：US10390438

申请日：2003-03-17

Applicant: Ravindra K. Pandey ,  Zachary Grossman ,  Peter Kanter ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Zachary Grossman ,  Peter Kanter ,  Thomas J. Dougherty

IPC: A61B5/055

CPC classification number: C07D487/22 ,  A61K49/085 ,  A61K49/103 ,  A61K51/0478 ,  A61K51/0485 ,  C07D471/22

Abstract: A method for MR imaging that comprises conducting the MR imaging after injecting compositions that are chemical combination of porphyrins, chlorins, bacteriochlorins, and related tetra-pyrrolic compounds with radioactive elements such as Technetium99, Gadolinium, Indium111 and radioactive iodine. When the element can form cations, the compound is usually a chelate with the porphyrin or chlorin structure. When the element forms anions, the compound is usually a direct chemical combination of the radioactive element into the porphyrin or chlorin structure. The method uses the compounds of the invention for diagnostic imaging of hyperproliferative tissue such as tumors and new blood vessel growth as is associated with the wet form of age related macular degeneration and methods of making the compounds. Compounds for MRI contrast imaging of the invention are usually Tc99, In111 or Gd(III) complexes of compounds of the formula:

Abstract translation: 一种用于MR成像的方法，其包括在注入组合物之后进行MR成像，所述组合物是卟啉，二氢卟酚，细菌二氢卟酚和相关的四吡咯化合物与放射性元素如锝99，钆， SUP> 111和放射性碘。 当元素可以形成阳离子时，化合物通常是具有卟啉或二氢卟酚结构的螯合物。 当元素形成阴离子时，化合物通常是放射性元素与卟啉或二氢卟酚结构的直接化学组合。 该方法使用本发明的化合物用于与增殖性组织例如肿瘤和新血管生长的诊断成像，其与湿性形式的年龄相关性黄斑变性相关联，以及制备该化合物的方法。 本发明的MRI造影成像的化合物通常为下式化合物的Tc 99，III 111或Gd（III）络合物：

公开(公告)号：US07053210B2

公开(公告)日：2006-05-30

申请号：US10613474

申请日：2003-07-02

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty ,  Alexander J. Pallenberg

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty ,  Alexander J. Pallenberg

IPC: A61B5/055 ,  A61B10/00 ,  C07B47/00 ,  C07F5/10 ,  A61K31/555

CPC classification number: C07D471/22 ,  C07D487/22 ,  C07D491/22

Abstract: A process for the preparation of pyropheophorbide a and its derivatives, including 3-devinyl-3-(1′-hexyloxy)ethyl-pyropheophorbide-a, otherwise known as HPPH, is provided. The process involves treating chlorin e6, in the form of its trimethyl ester, with a base, followed by heating to give pyropheophorbide a, which is converted to HPPH by treatment with acid, followed by hexyl alcohol under basic conditions.

Abstract translation: 提供了制备焦脱镁叶绿酸a及其衍生物的方法，包括3-脱乙烯基-3-（1'-己氧基）乙基 - 焦脱镁叶绿酸a，也称为HPPH。 该方法包括用碱处理其三甲酯形式的二氢卟酚，然后加热得到焦脱镁叶绿酸a，其通过用酸处理转化成HPPH，随后用己醇转化为HPPH 基本条件

公开(公告)号：US06849607B2

公开(公告)日：2005-02-01

申请号：US10141241

申请日：2002-05-07

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty

IPC: A61P35/00 ,  C07H15/18 ,  C07H15/26 ,  C07H23/00 ,  A01N43/04 ,  A61B5/055 ,  C07H15/00

CPC classification number: C07H15/18 ,  C07H15/26 ,  C07H23/00

Abstract: Purpurin-carbohydrate conjugates and their method of preparation and use for treatment of cancer cells. The conjugates have the general formula: wherein R6 and R7 taken together are ═NR11 or are independently —OR11, where at least one R11 is preferably a mono or polysaccharide moiety and R1-R8 are various groups formed from carbon and hydrogen and optionally oxygen and nitrogen where R3 and R4 may together from a covalent bond.

Abstract translation: 紫杉醇 - 碳水化合物缀合物及其制备和用于治疗癌细胞的方法。 缀合物具有以下通式：其中R 6和R 7一起为= NR 11或独立地为-OR 11，其中至少一个R 11优选为单糖或多糖部分，并且R 1 -R 8为由碳和氢以及任选的氧形成的各种基团， 氮，其中R3和R4可以共价键。

公开(公告)号：US06624187B1

公开(公告)日：2003-09-23

申请号：US09592150

申请日：2000-06-12

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty ,  William R. Potter

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty ,  William R. Potter

IPC: C07D48722

CPC classification number: C07D471/22 ,  C07D487/22 ,  C07D491/22

Abstract: Novel compounds that either preferentially absorb into hyperproliferative tissue and absorb light efficiently at a wavelength of between about 700 and about 850 nm or act as intermediates for such absorbing compounds. More particularly, the compounds of the invention have the formula: where R1, R5, R9, and R10 are independently lower alkyl of 1 to 3 carbon atoms provided that at least three of R1, R5, R9, and R10 are methyl; R2 is —OH, —OR11, —NHR11, aryl, or -aminoacid; R3 and R4 are independently —COR11 or taken together are R6 and R7 are independently lower alkyl of 1 to 3 carbon atoms; R8 is O-alkyl of 1 to about 12 carbon atoms, S-alkyl of 1 to about 12 carbon atoms, —O-aryl, or —O-heterocyclic ring of 5 or 6 carbon atoms; R11 is alkyl of 1 to 6 carbon atoms; and R12 is lower alkyl of 1 to about 12 carbon atoms, aryl, or aminoalkyl of 1 to 8 carbon atoms; provided that at least one of R8, R11, and R12 is hydrophobic and together contain at least 10 carbon atoms. The invention also includes method of making and using the compounds.

Abstract translation: 优先吸收过度增生组织并在约700至约850nm波长处有效吸收光的新型化合物或作为这种吸收化合物的中间体。 更具体地，本发明的化合物具有下式：其中R 1，R 5，R 9和R 10独立地为1至3个碳原子的低级烷基，条件是R R 1，R 5，R 9和R 10是甲基; R 2是-OH，-OR 11，-NHR 11，芳基或 - 氨基酸; R 3和R 4独立地为-COR 11或一起为R 6和R 7独立地为1至3个碳原子的低级烷基; R 8是1至约12个碳原子的O-烷基，1至约12个碳原子的S-烷基，具有5或6个碳原子的-O-芳基或-O-杂环; R 11是1至6个碳原子的烷基; 且R 12为1至约12个碳原子的低级烷基，1至8个碳原子的芳基或氨基烷基; 条件是R 8，R 11和R 12中的至少一个是疏水性的并且一起含有至少10个碳原子。 本发明还包括制备和使用该化合物的方法。

公开(公告)号：US5770730A

公开(公告)日：1998-06-23

申请号：US613134

申请日：1996-03-08

Applicant: Ravindra K. Pandey ,  Andrei N. Kozyrev ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Andrei N. Kozyrev ,  Thomas J. Dougherty

IPC: A61K41/00 ,  C07D471/22 ,  C07D491/22 ,  C07D487/22

CPC classification number: C07D471/22 ,  A61K41/0071 ,  C07D491/22

Abstract: A method for the preparation of an imide derivative of purpurin by reacting hexylamine with a chlorin or bacteriochlorin having a macrocycle with a six-membered anhydride ring fused thereto, said macrocycle containing a and b rings which may be saturated or unsaturated at R.sub.4 to R.sub.11 positions of the rings and which R.sub.4 and R.sub.11, positions may contain at least one group selected from the group consisting of hydrogen, hydroxy, formyl, substituted and unsubstituted alkyl, alkoxy, alkenyl, aryl and aryloxy wherein carbon containing groups may be substituted with a substituent selected from, hydroxy, phosphoro, carboxy, halo, sulfo, amino and ether, to obtain a purpurin derivative; and reacting the purpurin derivative with a carbodiimide to obtain the imide derivative of purpurin. The invention further includes novel imides made by the method.

Abstract translation: 通过使己胺与具有稠合六元酸酐环的大环的二氢卟酚或菌绿素反应来制备紫苏素的酰亚胺衍生物的方法，所述大环含有在R4至R11位置可饱和或不饱和的a和b环 的R 4和R 11可以含有选自氢，羟基，甲酰基，取代和未取代的烷基，烷氧基，烯基，芳基和芳氧基中的至少一个基团，其中含碳基团可以被取代基取代 选自羟基，磷酰基，羧基，卤素，磺基，氨基和醚，得到紫红素衍生物; 并将紫草素衍生物与碳二亚胺反应，得到紫红素的酰亚胺衍生物。 本发明还包括通过该方法制备的新颖的酰亚胺。

公开(公告)号：US5314905A

公开(公告)日：1994-05-24

申请号：US973174

申请日：1992-11-09

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty

IPC: A61K31/40 ,  A61K41/00 ,  A61K51/04 ,  A61P31/12 ,  A61P35/00 ,  C07D487/22 ,  C07D519/00

CPC classification number: C07D487/22 ,  A61K41/0071 ,  A61K51/0485 ,  C07D519/00 ,  A61K2123/00

Abstract: Conjugate are formed by covalently linking a target-specific compound to pyropheophorbide compound which conjugated are injected into a host and accumulate in tumor tissue to a higher degree than surrounding normal tissues. When the pyropheophorbide compound component of the conjugate is exposed to a particular wavelength of light the compound becomes cytotoxic destroying the tumor or diseased tissue without causing irreversible normal tissue damage. The pyropheophorbide compounds have been shown to have a variety of characteristics when used in photodynamic therapy. These characteristics are further improved when the compounds are bound to a target specific component such as a ligand capable of binding to a specific cellular receptor (e.g. growth hormones and growth factors) or an antibody capable of binding to a particular antigen.

Abstract translation: 共轭体通过将靶特异性化合物与焦磷酸脱氢化合物共价连接而形成，所述化合物与缀合物注入宿主中，并且在肿瘤组织中积聚到比周围正常组织更高的程度。 当缀合物的焦偏心复合物组分暴露于特定波长的光时，该化合物变得细胞毒性破坏肿瘤或患病组织而不引起不可逆的正常组织损伤。 已经显示焦磷酸脱氢化合物在用于光动力疗法中具有多种特征。 当化合物结合到靶特异性组分如能够结合特定细胞受体的配体（例如生长激素和生长因子）或能够结合特定抗原的抗体时，这些特征进一步改善。

公开(公告)号：US5198460A

公开(公告)日：1993-03-30

申请号：US822409

申请日：1992-01-17

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty

IPC: A61K31/40 ,  A61K31/409 ,  A61K41/00 ,  A61K51/04 ,  A61P9/10 ,  A61P17/06 ,  A61P17/12 ,  A61P31/04 ,  A61P31/10 ,  A61P31/12 ,  A61P35/00 ,  C07D487/22 ,  C07D519/00

CPC classification number: A61K51/0485 ,  A61K41/0071 ,  C07D487/22 ,  C07D519/00 ,  A61K2123/00

Abstract: Pyropheophorbide compounds are injected into a host and accumulate in tumor tissue to a higher degree than surrounding normal tissues. When the pyropheophorbide compounds are exposed to a particular wavelength of light the compounds become cytotoxic and destroy the tumor or diseased tissue without causing irreversible normal tissue damage. The pyropheophorbide compounds have shown improved results as compared to drugs currently used in photodynamic therapy. Further, they absorb light further in the red, optimizing tissue penetration and are retained in the skin for short time periods relative to other drugs used in photodynamic therapy.

Abstract translation: 将焦磷偏磷酸酯化合物注射到宿主中并在肿瘤组织中积聚到比周围正常组织更高的程度。 当焦偏磷酸酯化合物暴露于特定波长的光时，化合物变成细胞毒性并破坏肿瘤或患病组织而不引起不可逆的正常组织损伤。 与目前在光动力疗法中使用的药物相比，焦偏镁离子化合物显示出改善的结果。 此外，它们进一步吸收红色的光，优化组织穿透，并相对于光动力疗法中使用的其他药物，在短时间内保留在皮肤中。

公开(公告)号：US5190966A

公开(公告)日：1993-03-02

申请号：US584204

申请日：1990-09-18

Applicant: Thomas J. Dougherty ,  Ravindra K. Pandey

Inventor： Thomas J. Dougherty ,  Ravindra K. Pandey

IPC: A61K31/40 ,  A61K41/00 ,  C07D519/00

CPC classification number: C07D519/00 ,  A61K31/40 ,  A61K41/0071

Abstract: Pure dimer and trimer compounds of hematoporphyrin are prepared and shown to be effective agents in photodynamic therapy. The compounds of the invention are of the formula ##STR1## wherein each X is independently 1-hydroxyethyl or vinyl and wherein R is H or lower alkyl. The compounds of the invention can be conjugated to targeting substances such as immunoglobulins or to labels.

Abstract translation: 制备血卟啉的纯二聚体和三聚体化合物，并显示为光动力学治疗中的有效试剂。 本发明的化合物具有下式：其中每个X独立地是1-羟基乙基或乙烯基，并且其中R是H或更低的（R 1，R 2，R 3， 烷基。 本发明的化合物可以与靶向物质例如免疫球蛋白缀合，或与标记缀合。

公开(公告)号：US5093349A

公开(公告)日：1992-03-03

申请号：US597786

申请日：1990-10-15

Applicant: Ravindra K. Pandey ,  Thomas J. Dougherty

Inventor： Ravindra K. Pandey ,  Thomas J. Dougherty

IPC: A61K41/00 ,  C07D487/22 ,  C07D519/00

CPC classification number: C07D487/22 ,  A61K41/0071 ,  C07D519/00

Abstract: New classes of photosensitizing compounds useful in photodynamic therapy are disclosed. These compounds are simplified dimers and polymers of monohydroxy deuteroporphyrins, hydrophobic ethers of these monomers, and red light-absorbing derivatives of methyl pheophorbide-a.

Abstract translation: 公开了可用于光动力学治疗的新类型的光敏化合物。 这些化合物是简单的二聚体和单羟基氘卟啉的聚合物，这些单体的疏水性醚，以及脱镁叶绿酸甲酯的红光吸收衍生物。

公开(公告)号：US08198432B2

公开(公告)日：2012-06-12

申请号：US12462535

申请日：2009-08-05

Applicant: Ravindra K. Pandey ,  Munawwar Sajjad ,  Suresh Pandey ,  Amy Gryshuk ,  Allan Oseroff ,  Stephanie Pincus, legal representative ,  Hani A. Nabi

Inventor： Ravindra K. Pandey ,  Munawwar Sajjad ,  Suresh Pandey ,  Amy Gryshuk ,  Allan Oseroff ,  Hani A. Nabi

IPC: C07B47/00 ,  C07D487/22

CPC classification number: C07D487/22 ,  A61K51/0485 ,  C07H17/02

Abstract: 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.

Abstract translation: 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。