Gregory W Hemmi

US Patent:

56329709, May 27, 1997

Filed:

Jun 7, 1995

Appl. No.:

8/486967

Inventors:

Jonathan L. Sessler - Austin TX
Tarak D. Mody - Sunnyvale CA
Gregory W. Hemmi - Sunnyvale CA
Vladimir A. Kr al - Austin TX
Darren Magda - Cupertino CA

Assignee:

Board of Regents, The University of Texas - Austin TX
Pharmacyclics, Inc. - Sunnyvale CA

International Classification:

A61K 31555

US Classification:

424 961

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 biolocatization, and iv) indifference to the presence or absence of O. sub. 2. 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.

US Patent:

56018029, Feb 11, 1997

Filed:

Jun 7, 1995

Appl. No.:

8/486886

Inventors:

Gregory W. Hemmi - Sunnyvale CA
Jonathan L. Sessler - Austin TX
Tarak D. Mody - Sunnyvale CA

Assignee:

Pharmacyclics, Inc. - Sunnyvale CA
Board of Trustees, Univ. of TX Sys. - Austin TX

International Classification:

C07D22500
G01N 2408

US Classification:

424 9363

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. These texaphyrin metal complexes having enhanced stability are useful for localization, magnetic resonance imaging, radiosensitization, radiation therapy, fluorescence imaging, photodynamic therapy, RNA hydrolysis, DNA photocleavage, and applications requiring singlet oxygen production for cytotoxicity. 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.

US Patent:

55999280, Feb 4, 1997

Filed:

Jun 2, 1995

Appl. No.:

8/459333

Inventors:

Gregory W. Hemmi - Sunnyvale CA
Jonathan L. Sessler - Austin TX
Tarak D. Mody - Sunnyvale CA

Assignee:

Pharmacyclics, Inc. - Sunnyvale CA
Board of Regents, The University of Texas System - Austin TX

International Classification:

C07D48722

US Classification:

540474

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.

US Patent:

55873715, Dec 24, 1996

Filed:

Jun 2, 1995

Appl. No.:

8/458909

Inventors:

Jonathan L. Sessler - Austin TX
Tarak D. Mody - Sunnyvale CA
Gregory W. Hemmi - Sunnyvale CA
Vladimir A. Kr al - Austin TX
Darren Magda - Cupertino CA

Assignee:

Pharmacyclics, Inc. - Sunnyvale CA
Board of Trustees, Univ. of TX Sys. - Austin TX

International Classification:

A61K 31715
C07D48722

US Classification:

514185

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 O. sub. 2. 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.

US Patent:

58889973, Mar 30, 1999

Filed:

Feb 4, 1997

Appl. No.:

8/795393

Inventors:

Jonathan L. Sessler - Austin TX
Anthony Harriman - Bischheim, FR
Richard A. Miller - Portola Valley CA
Darren Magda - Cupertino CA
Tarak D. Mody - Sunnyvale CA
Gregory W. Hemmi - Sunnyvale CA

Assignee:

Pharmacyclics, Inc. - Sunnyvale CA
Board of Regents, The University of Texas System - Austin TX

International Classification:

A61K 31555

US Classification:

514185

Abstract:

The invention relates to the field of radiation sensitizers and the use of texaphyrins for radiation sensitization and other conditions for which X-ray radiation has proven to be therapeutic.

US Patent:

60691409, May 30, 2000

Filed:

Nov 14, 1997

Appl. No.:

8/970864

Inventors:

Jonathan L. Sessler - Austin TX
Tarak D. Mody - Sunnyvale CA
Gregory W. Hemmi - Sunnyvale CA

Assignee:

The Board of Regents University of Texas System - Austin TX

International Classification:

A61K 3140

US Classification:

514185

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 O. sub. 2. 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.

US Patent:

58861734, Mar 23, 1999

Filed:

Jul 30, 1997

Appl. No.:

8/903121

Inventors:

Gregory W. Hemmi - Sunnyvale CA
Miguel Rosingana - San Francisco CA

Assignee:

Pharmacyclics, Inc. - Sunnyvale CA

International Classification:

C07D48722
C07D25700

US Classification:

540472

Abstract:

A method has been developed which utilizes a metal-2,4-dicarbonyl complex as an organic solvent soluble metal ion source in the metallation of polyazamacrocycles including porphyrins, expanded porphyrins and porphyrinoid compounds. Use of a metal ion source which is soluble in the metallation reaction medium produces significantly higher yields of a measurably purer product than is achieved using an insoluble or only sparingly soluble metal salt as in the prior art. Additionally, because the metallation can be performed in relatively concentrated mixtures, the reaction times are dramatically shorter and the amount of waste produced is less than when simple metal salts serve as the metal ion source. Further, use of the soluble metal-2,4-dicarbonyl complex simplifies the purification protocol required for the metallated expanded porphyrin.

US Patent:

58012290, Sep 1, 1998

Filed:

Sep 13, 1996

Appl. No.:

8/713701

Inventors:

Jonathan L. Sessler - Austin TX
Tarak D. Mody - Sunnyvale CA
Gregory W. Hemmi - Sunnyvale CA
Vladimir A. Kral - Austin TX

Assignee:

The Board of Regents, University of Texas System - Austin TX

International Classification:

C07D48722

US Classification:

534 15

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 O. sub. 2. 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.