Anthracene-9, 10-dione dioxime compound prodrugs and their uses
Chemical agents, such as disulfonamide derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine, and similar heterocyclic ring structures; including, salts thereof that act as anti-cancer and anti-tumor agents, along with methods for preparing such agents, as well as pharmaceutical compositions containing such agents as active ingredients and methods of using these as therapeutic agents.
1. A compound having the following formula:
wherein
R 5 is selected from the group consisting of H, —P(O)(OH) 2 , —CHR 7 —O—P(O)(OH) 2 , —C(O)—R 8 , and —CHR 7 —O—C(O)—R 8 ;
R 6 is selected from the group consisting of —P(O)(OH) 2 ; CHR 7 —O—P(O)(OH) 2 , —C(O)—R 8 , and —CHR 7 —O—C(O)—R 8 ;
R 7 is H or an optionally substituted lower alkyl;
R 8 is a lower alkyl, —OR 11 , -aryl, heteroaryl or heterocycloalkyl, wherein said lower alkyl, aryl, heteroaryl or heterocycloalkyl is optionally substituted with —NR 9 R 10 and/or OR 12 ;
R 9 and R 10 are independently selected from the group consisting of H, —P(O)(OH) 2 , and optionally substituted lower alkyl or can optionally combine with OR 12 to form a 5- to 7-membered heterocycloalkyl,
R 11 is independently selected from the group consisting of lower alkyl, aryl, heteroaryl and heterocycloalkyl wherein said lower alkyl, aryl, heteroaryl or heterocycloalkyl is optionally substituted with —NR 9 R 10 and/or —OH; and
R 12 is H or —P(O)(OH) 2 , or
a geometric isomer, a stereoisomer, an enantiomer, a diastereomer, a tautomer, or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound has the following structure:
3. A compound selected from a group consisting of:
or a geometric isomer, a stereoisomer, an enantiomer, a diastereomer, a tautomer, or a pharmaceutically acceptable salt thereof.
4. A method of treating or ameliorating cancer or tumor metastasis in a mammal in need thereof comprising administering to said mammal an effective amount of a compound of claim 1 .
5. A method for treating cancer comprising administering to a subject in need thereof a combination of: 1) a pharmaceutically effective amount of a compound of claim 1 ; and 2) a pharmaceutically effective amount of at least one additional anti-cancer agent.
6. The method of claim 5 , wherein the additional anti-cancer agent is selected from the group consisting of antimitotic agents, antimetabolite agents, HDAC inhibitors, proteosome inhibitors, immunotherapeutic agents, FLT-3 kinase inhibitors, and WNT pathway inhibitors.