Sanofi-Synthelabo

Cancer Therapy and Research Center

Daniel L Dexter

Alexander L Weis

Shih-Fong Chen

Daniel D Von Hoff

Paul E Juniewicz

James B Rake

Mallaiah Mittakanti

Peech S Reddy

Peech S Reedy

Jan M Woynarowski

Method of treating a tumor

In accordance with the present invention there is provided a method of treating a mammal having a solid tumor, the method comprising:

The present invention provides novel bis-naphthalimides characterized by having a linker containing a heteroatom, their preparation, pharmaceutical compositions thereof, and various methods of using the bis-naphthalimides. Particularly preferred bis-naphthalimides have a linker of about 8-16 atoms where the heteroatom is oxygen, sulfur, sulfur oxide or sulfur dioxide. The bis-naphthalimides provided herein have exceptional DNA binding properties and demonstrate cytotoxicity in both in vitro and in vivo tumor models, in particular, against melanoma.

Unsymmetrically linked bisnaphthalimides as antitumor agents

The present invention provides novel bis-naphthalimides characterized by having a linker containing a heteroatom, their preparation, pharmaceutical compositions thereof, and various methods of using the bis-naphthalimides. Particularly preferred bis-naphthalimides have a linker of about 8-16 atoms where the heteroatom is oxygen, sulfur, sulfur oxide or sulfur dioxide. The bis-naphthalimides provided herein have exceptional DNA binding properties and demonstrate cytotoxicity in both in vitro and in vivo tumor models, in particular, against melanoma. Also provided a novel mono-naphthalimides linked to a DNA alkylating agent. These agents are shown to have conformational effects on double stranded DNA and to form covalent adducts after an extended incubation period.

Diamine platinum naphthalimide complexes as antitumor agents

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Holcombe, WI, United States of America

Daniel L Dexter