公开(公告)号：JP2004091495A

公开(公告)日：2004-03-25

申请号：JP2003377620

申请日：2003-11-06

Applicant: Pharmacyclics Inc ,  Univ Texas Syst ,  ファーマサイクリクス,インコーポレイテッド ,  ボード オブ リージェンツ, ザ ユニバーシティ オブ テキサス システムBoard Of Regents,The University Of Texas System

Inventor： SESSLER JONATHAN L ,  HARRIMAN ANTHONY M ,  MILLER RICHARD A ,  MODY TARAK D ,  HEMMI GREGORY W ,  KRAAL VLADIMIR A ,  MAGDA DARREN

IPC: A61K31/40 ,  A61K31/407 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/02 ,  A61P43/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07D487/22 ,  C07H21/00

CPC classification number: A61K51/0485 ,  A61K41/0038 ,  A61K41/0057 ,  A61K41/0076 ,  A61K47/546 ,  A61K49/0021 ,  A61K49/0054 ,  A61K49/085 ,  A61K49/10 ,  A61K49/106 ,  A61K49/126 ,  A61L2/0011 ,  B01J31/061 ,  B01J31/1658 ,  B01J31/1805 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/23 ,  B01J2531/26 ,  B01J2531/27 ,  B01J2531/28 ,  B01J2531/36 ,  B01J2531/37 ,  B01J2531/38 ,  B01J2531/72 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  B01J2531/96 ,  C07D487/22 ,  C07H21/00

Abstract: PROBLEM TO BE SOLVED: To obtain texaphyrin for radiosensitization. SOLUTION: A medicinal composition used for a radiosensitizer is prepared by using the texaphyrin. The texaphyrin is an aromatic 5 position (and heptacyclic) macrocycle (enlarged porphyrin) and, may be due to its inherent lipophilic property, shows larger biolocalization in non-neoplasm organs and non-atheroma plaque in neoplasm organ and atheroma each possible to be a malignant or benign tumor. The texaphyrin improves radiation damage and overcomes many defects of conventional radiosensitizers. COPYRIGHT: (C)2004,JPO

公开(公告)号：WO9429316A3

公开(公告)日：1995-02-02

申请号：PCT/US9406284

申请日：1994-06-09

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC ,  SESSLER JONATHAN L ,  ROSS KEVIN L ,  WRIGHT MEREDITH ,  HEMMI GREGORY W ,  DOW WILLIAM C ,  SMITH DANIEL A ,  KRAL VLADIMIR A ,  IVERSON BRENT ,  MODY TARAK ,  MILLER RICHARD A ,  MAGDA DARREN

Inventor： SESSLER JONATHAN L ,  ROSS KEVIN L ,  WRIGHT MEREDITH ,  HEMMI GREGORY W ,  DOW WILLIAM C ,  SMITH DANIEL A ,  KRAL VLADIMIR A ,  IVERSON BRENT ,  MODY TARAK ,  MILLER RICHARD A ,  MAGDA DARREN

IPC: A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/04 ,  A61L2/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07B61/00 ,  C07D487/22 ,  C07F9/06 ,  C07F9/6558 ,  C07F9/6561 ,  C07H21/00 ,  C12N15/10 ,  C12Q1/68

CPC classification number: C07D487/22 ,  A61K41/0038 ,  A61K41/0076 ,  A61K47/546 ,  A61K49/0021 ,  A61K49/0036 ,  A61K49/085 ,  A61K49/106 ,  A61K49/126 ,  A61K51/0485 ,  A61L2/0011 ,  B01J31/061 ,  B01J31/1658 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/23 ,  B01J2531/26 ,  B01J2531/27 ,  B01J2531/28 ,  B01J2531/38 ,  B01J2531/72 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  B01J2531/96 ,  C07H21/00

Abstract: A method of phosphate ester hydrolysis including incubating a solution of an aqueous phosphate ester with a texaphyrin metal complex. The metal is a metal cation having catalytic activity for ester bond hydrolysis in aqueous solution, in particular, a lanthanide metal cation, preferably Eu(III) or Dy(III). A preferred substrate is RNA and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directed molecule, preferably an oligonucleotide.

公开(公告)号：ES2193163T3

公开(公告)日：2003-11-01

申请号：ES94931812

申请日：1994-10-12

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： SESSLER JONATHAN L ,  HARRIMAN ANTHONY M ,  MILLER RICHARD A ,  MODY TARAK D ,  HEMMI GREGORY W ,  KRAL VLADIMIR A

IPC: A61K31/40 ,  A61K31/407 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/02 ,  A61P43/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07D487/22 ,  C07H21/00 ,  A61P35/00

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

公开(公告)号：PT745085E

公开(公告)日：2002-10-31

申请号：PT95911776

申请日：1995-02-15

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： SESSLER JONATHAN L ,  MODY TARAK D ,  HEMMI GREGORY W

IPC: A61K31/40 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/00 ,  C07D487/22 ,  C07H21/00

Abstract: Texaphyrin metal complexes having improved functionalization include the addition of electron-donating groups to positions 2, 7, 12, 15, 18 and/or 21 and/or the addition of electron-withdrawing groups to positions 15 and/or 18 of the macrocycle. Electron-donating groups at positions 2, 7, 12, 15, 18 and/or 21 contribute electrons to the aromatic pi system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis. The addition of substituents to the 12 and 21 positions of the macrocycle offer steric protection for the imine bonds against possible in vivo enzyme hydrolysis. Electron-withdrawing groups at positions 15 and/or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential and imine bond stabilization are useful in a variety of applications.

公开(公告)号：SG48392A1

公开(公告)日：1998-04-17

申请号：SG1996009309

申请日：1994-10-12

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： HARRIMAN ANTHONY M ,  HEMMI GREGORY W ,  KRAL VLADIMIR A ,  MAGDA DARREN ,  MILLER RICHARD A ,  MODY TARAK D ,  SESSLER JONATHAN L

IPC: A61K31/40 ,  A61K31/407 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/02 ,  A61P43/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07D487/22 ,  C07H21/00

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

公开(公告)号：NO971317D0

公开(公告)日：1997-03-20

申请号：NO971317

申请日：1997-03-20

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： MAGDA DARREN ,  SESSLER JONATHAN L ,  IVERSON BRENT L ,  SANSOM PETRA I ,  WRIGHT MEREDITH ,  MODY TARAK D ,  HEMMI GREGORY W

IPC: A61K31/70 ,  C12N15/09 ,  A61K38/00 ,  A61K38/22 ,  A61K39/395 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/04 ,  A61L2/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07D487/22 ,  C07H21/00 ,  C07H21/04 ,  C12N15/113

Abstract: Methods of cleavage of a polymer of deoxyribonucleic acid using photosensitive texaphyrins are disclosed. A preferred method of use is the site-specific cleavage of a polymer of deoxyribonucleic acid and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directing molecule, preferably an oligonucleotide.

公开(公告)号：CA2200571A1

公开(公告)日：1996-03-28

申请号：CA2200571

申请日：1995-09-21

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： MAGDA DARREN ,  SESSLER JONATHAN L ,  IVERSON BRENT L ,  SANSOM PETRA I ,  WRIGHT MEREDITH ,  MODY TARAK D ,  HEMMI GREGORY W

IPC: C12N15/09 ,  A61K31/70 ,  A61K38/00 ,  A61K38/22 ,  A61K39/395 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/04 ,  A61L2/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07D487/22 ,  C07H21/00 ,  C07H21/04 ,  C12N15/113 ,  C07H23/00 ,  C12N13/00 ,  C12N9/16 ,  C12N9/96

Abstract: Methods of cleavage of a polymer of deoxyribonucleic acid using photosensitive texaphyrins are disclosed. A preferred method of use is the site-specific cleavage of a polymer of deoxyribonucleic acid, and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directing molecule, preferably an oligonucleotide.

公开(公告)号：CA2173319C

公开(公告)日：2008-03-25

申请号：CA2173319

申请日：1994-10-12

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： SESSLER JONATHAN L ,  HARRIMAN ANTHONY M ,  MILLER RICHARD A ,  MODY TARAK D ,  HEMMI GREGORY W ,  KRAL VLADIMIR A ,  MAGDA DARREN

IPC: C07D487/22 ,  A61K31/40 ,  A61K31/407 ,  A61K31/555 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/02 ,  A61P43/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07H21/00

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

公开(公告)号：AT233575T

公开(公告)日：2003-03-15

申请号：AT94931812

申请日：1994-10-12

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： SESSLER JONATHAN L ,  HARRIMAN ANTHONY M ,  MILLER RICHARD A ,  MODY TARAK D ,  HEMMI GREGORY W ,  KRAL VLADIMIR A ,  MAGDA DARREN

IPC: A61K31/40 ,  A61K31/407 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/02 ,  A61P43/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07D487/22 ,  C07H21/00 ,  A61P35/00

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

公开(公告)号：AU688008B2

公开(公告)日：1998-03-05

申请号：AU1921795

申请日：1995-02-15

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC

Inventor： SESSLER JONATHAN L ,  MODY TARAK D ,  HEMMI GREGORY W

IPC: A61K31/40 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/00 ,  A61K51/04 ,  A61L2/00 ,  A61P35/00 ,  C07D487/22 ,  C07H21/00

Abstract: Texaphyrin metal complexes having improved functionalization include the addition of electron-donating groups to positions 2, 7, 12, 15, 18 and/or 21 and/or the addition of electron-withdrawing groups to positions 15 and/or 18 of the macrocycle. Electron-donating groups at positions 2, 7, 12, 15, 18 and/or 21 contribute electrons to the aromatic pi system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis. The addition of substituents to the 12 and 21 positions of the macrocycle offer steric protection for the imine bonds against possible in vivo enzyme hydrolysis. Electron-withdrawing groups at positions 15 and/or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential and imine bond stabilization are useful in a variety of applications.