Diazeniumdiolated compounds, pharmaceutical compositions, and method of treating cancer

A compound of the formula (Ib) or (Ic), wherein the compound of formula (Ib) has the following structure:

• wherein R1 is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl alkyl, aryl, heterocyclic, heteroaryl, and heteroaryl alkyl, each of which is optionally substituted with a substituent selected from the group consisting of halo, OH, CN, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, aryloxy, thioalkoxy, nitro, sulfonato, formyl, acyl, acyloxy, carboxyl, mercapto, alkoxycarbonyl, alkoxycarbonyloxy, amido, amino, alkylamino, and dialkylamino;
• and
• R2 to R9 are independently selected from the group consisting of H, halo, alkyl, alkenyl, alkynyl, aryl alkyl, aryl, heterocyclic, heteroaryl, heteroaryl alkyl, OH, CN, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, aryloxy, thioalkoxy, nitro, sulfonato, formyl, acyl, acyloxy, carboxyl, mercapto, alkoxycarbonyl, alkoxycarbonyloxy, amido, amino, alkylamino, and dialkylamino;
• X1 and X2 are independently nitro or cyano;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that when all of R2 to R9 are H and X1 and X2 are both nitro, then R1 is not an unsubstituted alkyl group, and
• the compound of formula (Ic) has the following structure:
• wherein R1 is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl alkyl, aryl, heterocyclic, heteroaryl, and heteroaryl alkyl, each of which is optionally substituted with a substituent selected from the group consisting of halo, OH, CN, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, aryloxy, thioalkoxy, nitro, sulfonato, formyl, acyl, acyloxy, carboxyl, mercapto, alkoxycarbonyl, alkoxycarbonyloxy, amido, amino, alkylamino, and dialkylamino;
• and
• R2 to R9 are independently selected from the group consisting of H, halo, alkyl, alkenyl, alkynyl, aryl alkyl, aryl, heterocyclic, heteroaryl, heteroaryl alkyl, OH, CN, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, aryloxy, thioalkoxy, nitro, sulfonato, formyl, acyl, acyloxy, carboxyl, mercapto, alkoxycarbonyl, alkoxycarbonyloxy, amido, amino, alkylamino, and dialkylamino;
• X1 and X2 are independently nitro or cyano;
• wherein at least one of X1 and X2 is cyano;
• n is 0 or 1;
• or a pharmaceutically acceptable salt thereof.

A method of enhancing chemotherapeutic treatment of cancer with a chemotherapeutic agent that produces reactive oxygen species (ROS) in the cancer cell or radiation treatment of cancer, the method comprising administering an effective amount of a diazeniumdiolated compound of the formula (I):

• wherein
• X is selected from the group consisting of amino, alkylamino, dialkylamino, arylamino, diarylamino, a polyamino, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl,
• Q is an aryl, heteroaryl, or heterocyclyl, and
• wherein X is optionally substituted with one or more moieties selected from the group consisting of —[N(NO)O31 ], halo, hydroxy, alkylthio, arylthio, alkoxy, aryloxy, amino, alkylamino, dialkylamino, nitroso, cyano, sulfonato, mercapto, nitro, oxo, alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl alkyl, aryl, benzylcarbonyl, phenylcarbonyl, phosphono, and phosphato, and
• Q is optionally substituted with one or more moieties selected from the group consisting of —[N(NO)O−], halo, hydroxy, alkylthio, arylthio, alkoxy, aryloxy, amino, alkylamino, dialkylamino, nitroso, cyano, sulfonato, mercapto, nitro, oxo, alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl alkyl, aryl, benzylcarbonyl, phenylcarbonyl, phosphono, phosphato, and X[N(O)NO]−;
• or a pharmaceutically acceptable salt thereof.