Tricyclic [1,2,4]Triazine 1,4-Dioxides As Hypoxia Selective Cytotoxins

Sulfoxide-containing aromatic nitrogen mustards as hypoxia-directed bioreductive cytotoxins.

A series of diaryl and alkylaryl sulfoxide-containing nitrogen mustards were synthesized and evaluated for their hypoxia-selective cytotoxicity against V-79 cells in vitro as well as for their metabolism profiles with the rat S-9 fractions. In general, the diaryl sulfoxides (4, 5, and 7-9) showed much greater hypoxia selectivity (11-27-fold) than the alkylaryl sulfoxides (approximately 3-fold) ...

Targeting tumors with hypoxia-activated cytotoxins.

This review focuses on the recent development of hypoxia-activated cytotoxins. Such drugs are prodrugs activated to cytotoxic products in the hypoxic environment of solid tumors (so-called "bioreductive prodrugs"), but can also be activated by radiation (radiation-activated prodrugs). These compounds grew out of research on hypoxic radiosensitizers, which are compounds that can overcome the rad...

Modifying the glycosidic linkage in digitoxin analogs provides selective cytotoxins.

A chemoselective reaction between oxyamines and unprotected, unactivated reducing sugars was used to construct for the first time a panel of linkage-diversified neoglycosides. This panel of digitoxin analogs included potent and selective tumor cytotoxins; cytotoxicity was dependent on the structure of the glycosidic linkage. These results validate linkage diversification through neoglycosylatio...

Synthesis of selective SRPK-1 inhibitors: novel tricyclic quinoxaline derivatives.

SR protein-specific kinase-1 (SRPK-1) has been identified as a validated target for hepatitis B virus (HBV). A series of novel tricyclic quinoxaline derivatives was designed and synthesised as potential kinase inhibitory antiviral agents and was found to be active and selective for SRPK-1 kinase. Most of these novel compounds have drug-like properties according to experimentally determined LogP...

Highly selective disaccharide recognition by a tricyclic octaamide cage.