Sri International

Other

Edward W Grange

William W Lee

J Martin Brown

Abelardo P Martinez

Daniel J Pollart

Michael Tracy

David W Henry

Kenneth J Ryan

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

1,2,4-Benzotriazine oxides as radiosensitizers and selective cytotoxic agents

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitive hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

1, 2, 4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents

1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosentitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4- benzotriazine oxides is also disclosed.

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed no be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.

A method for radiosensitizing hypoxic tumor cells in a warm-blooded animal is provided. The method involves administration of a nicotinamide compound having the structural formula ##STR1## wherein X is O or S, and Z is H, OR, SR or NHR where R is as defined herein. Exemplary compounds for use in conjunction with the disclosed method include: 5-hydroxynicotinamide; 5-hydroxynicotinamide, sodium salt; 5-(2,3-dihydroxypropoxy)nicotinamide; 5-aminonicotinamide; 5-(2-methoxyethylamino)nicotinamide; and 5-acetamidonicotinamide.

Benzamide and nicotinamide radiosensitizers

Process for preparing 1,2,4-benzotriazine oxides

A method for sensitizing hypoxic tumor cells to radiation using derivatives of benzamide are disclosed. Some of the compounds useful in the method of the invention are novel.

Substituted benzamide radiosensitizers

A method for sensitizing hypoxic tumor cells to radiation using derivatives of benzamide are disclosed. Some of the compounds useful in the

Mesoionic anhydro-5-amino-1,2,3,4-oxatriazolium hydroxides and methods of using the same in the treatment of cancer, said compositions containing, as an active ingredient, one or more compounds having the structure ##STR1## wherein R.sup.1 represents a phenyl or substituted phenyl group and R.sup.2 represents hydrogen or a methyl group.

Mesoionic antitumor compositions and methods for using the same in the

Glyoxylic acid hydrocarbylsulfonylhydrazones and therapeutic compositions containing the same. Said compounds are useful in treating cancer, they being active against leukemia P-388, for example.

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Palo Alto, CA, United States of America

Edward W Grange