Sri International

Michael Tracy

William W Lee

Daniel J Pollart

Edward W Grange

J Martin Brown

Abelardo P Martinez

Edward M Acton

Kenneth J Ryan

Andrew B Kelson

Eric O Aboagye

Alexander D Lewis

Paul Workman

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

Agents useful for detecting hypoxic tumor cells are provided. The compounds have the structural formula (I) ##STR1## Methods of using the compounds to detect hypoxic tumor cells are also provided, as are pharmaceutical compositions formulated with the novel compounds.

Fluorinated 2-nitroimidazole analogs for detecting hypoxic tumor cells

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.

Process for preparing 1,2,4-benzotriazine oxides

Disclosed herein is a new procedure for preparing the C.1-2,4-pentadienyl derivatives of 2-deoxyhexopyranoses, as well as a new procedure for allylation of daunosamine. These methods are particularly useful for the preparation of intermediates in the synthesis of adriamycin C-glycosidic analogs which are useful anti-tumor agents. These methods provide the first enabling disclosure of methods to prepare these desired adriamycin and anthrocyclinone C-glycosidic analogs.

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Palo Alto, CA, United States of America

Michael Tracy