Abstract: Disclosed is a method of treating cancer in a patient comprising administering to the patient an effective amount of a diazeniumdiolated (N2O2-containing) compound or a pharmaceutically acceptable salt thereof, wherein the cancer cell has an elevated level of reactive oxygen species (ROS) and/or a decreased level of one or more of PRX1, PRX6, and OGG1, compared to a normal cell of the same tissue or tissue type. An example of a diazeniumdiolated compound is Formula (I), wherein X and Q are defined herein. Also disclosed are diazeniumdiolated compounds, pharmaceutical compositions, and methods of use including enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation.

Abstract: Disclosed are hybrid compounds that release both nitric oxide and a moiety that inhibits poly (ADP-ribose) polymerase (PARP), e.g., a compound or a pharmaceutically acceptable salt thereof of formula (I), wherein R1-4 and m-p are as described herein. Also disclosed are pharmaceutical compositions and methods of use including treating cancer and enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation.

Abstract: Disclosed are hybrid compounds that release both nitric oxide and a moiety that inhibits poly (ADP-ribose) polymerase (PARP), e.g., a compound or a pharmaceutically acceptable salt thereof of formula (I), wherein R1-4 and m-p are as described herein. Also disclosed are pharmaceutical compositions and methods of use including treating cancer and enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation.

Abstract: Disclosed is a compound of the formula (I) or a pharmaceutically acceptable salt thereof: (I) in which R1, R2, R3, and R4 are defined herein and pharmaceutical compositions thereof. Further provided is a method of treating various disorders, such as a disorder selected from the group consisting of a cardiovascular disorder, cancer, chronic pain, alcohol dependence, and inflammation in a patient comprising administering an effective amount of a compound or pharmaceutically acceptable salt of formula (I).

Abstract: Disclosed is a compound of the formula (I) or a pharmaceutically acceptable salt thereof: (I) in which R1, R2, R3, and R4 are defined herein and pharmaceutical compositions thereof. Further provided is a method of treating various disorders, such as a disorder selected from the group consisting of a cardiovascular disorder, cancer, chronic pain, alcohol dependence, and inflammation in a patient comprising administering an effective amount of a compound or pharmaceutically acceptable salt of formula (I).

Abstract: Disclosed is a method of treating cancer in a patient comprising administering to the patient an effective amount of a diazeniumdiolated (N2O2-containing) compound or a pharmaceutically acceptable salt thereof, wherein the cancer cell has an elevated level of reactive oxygen species (ROS) and/or a decreased level of one or more of PRX1, PRX6, and OGG1, compared to a normal cell of the same tissue or tissue type. An example of a diazeniumdiolated compound is Formula (I), wherein X and Q are defined herein. Also disclosed are diazeniumdiolated compounds, pharmaceutical compositions, and methods of use including enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation.

Abstract: Methods for enhancing detection by mass spectroscopy (MS) and/or chromatographic separability of carbonyl-containing compounds such as steroids are disclosed. Reaction of a carbonyl compound with a sulfonhydrazide compound provides a sulfonhydrazone with enhanced ionization efficiency during the electrospray ionization process. In a particularly disclosed embodiment, derivatization of catechol estrogens with p-toluenesulfonhydrazide enhances both detection by atmospheric pressure ionization-MS (API-MS), such as electron spray ionization-MS (ESI-MS) and separation by liquid chromatography (such as HPLC) under reverse phase conditions. In yet other embodiments, the sulfonhydrazone is further reacted with a sulfonyl halide under alkaline conditions to derivatize hydroxyl groups in the compound. Prior formation of the sulfonhydrazide derivative protects the carbonyl bond of the compound during subsequent alkaline reaction with the sulfonyl halide.

Abstract: Disclosed are compounds that release nitric oxide, e.g., a compound of Formula (I) wherein R1-10, X, and n are as described herein, which are NSAID derivatives comprising a diazeniumdiolate moiety N2O2?. The compounds are chemopreventive agents with gastric-sparing, analgesic, cardioprotective, and/or anti-inflammatory properties. Also disclosed is a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier. Also disclosed is a method of preventing or treating cancer or treating inflammation or an inflammation-related condition in a mammal comprising administering an effective amount of a compound of the invention to the mammal.

Abstract: The present invention provides O2-substituted 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates (1-[(2-carboxylato)pyrrolidin-1-yl]diazeniumdiolates) of the formula in which R and R22are as described herein. Also provided is a composition comprising such a compound and a carrier. The 1-[(2-carboxylato)pyrrolidin-1-yl]diazeniumdiolates compounds release nitric oxide under physiological conditions and are useful for treating biological disorders.

Abstract: Provided are O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates (O2-glycosylated diazeniumdiolates) having the formula: in which R is a saccharide, which is attached to the O2 of the compound by the anomeric carbon of a pyranose ring or a furanose ring.

Abstract: Diazeniumdiolates, wherein the N1 position is substituted by an inorganic or organic moiety and the O2-oxygen is bound to a substituted or unsubstituted aromatic group, are provided. Also provided are O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates (O2-glycosylated diazeniumdiolates) and O2-substituted 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates (1-[(2-carboxylato)pyrrolidin-1-yl]diazeniumdiolates). The O2-aryl diazeniumdiolates are stable with respect to the hydrolytic generation of nitric oxide in neutral to acidic solutions and generate nitric oxide in basic or nucleophilic environments or microenvironments. Also provided are compositions, including pharmaceutical compositions, comprising such compounds and methods of using such compounds.

Abstract: Diazeniumdiolates, wherein the N1 position is substituted by an inorganic or organic moiety and the O2-oxygen is bound to a substituted or unsubstituted aromatic group, are provided. Also provided are O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates (O2-glycosylated diazeniumdiolates) and O2-substituted 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates (1-[(2-carboxylato)pyrrolidin-1-yl]diazeniumdiolates). The O2-aryl diazeniumdiolates are stable with respect to the hydrolytic generation of nitric oxide in neutral to acidic solutions and generate nitric oxide in basic or nucleophilic environments or microenvironments. Also provided are compositions, including pharmaceutical compositions, comprising such compounds and methods of using such compounds.

Abstract: A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N2O2− functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Abstract: A method of treatment for impotency is provided. The method involves the administration of nitric oxide by a nitric oxide-releasing agent capable of providing a penile erection-inducing amount of nitric oxide to the corpus cavernosum of the penis of an impotent male animal. Also provided is a nitric oxide delivery means for use in the method.

Abstract: A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N2O2− functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Abstract: A method of treatment for impotency is provided. The method involves the administration of nitric oxide by a nitric oxide-releasing agent capable of providing a penile erection-inducing amount of nitric oxide to the corpus cavernosum of the penis of an impotent male animal. Also provided is a nitric oxide delivery means for use in the method.

Abstract: A method for the treatment of mammalian tissue injured or at risk of injury during sepsis or shock including the administration to a mammal a diazeniumdiolate which releases a therapeutically effective amount of nitric oxide sufficient to protect the tissue from sepsis- or shock-induced injury.

Abstract: There are disclosed N-substituted piperazine NONOate compounds having the structure: ##STR1## wherein M is a pharmaceutically acceptable cation, x is the valence of the cation, and R is selected from the group consisting of: an unsubstituted or substituted C.sub.1 -C.sub.20 straight chain alkyl, an unsubstituted or substituted C.sub.3 -C.sub.20 branched chain alkyl,an unsubstituted or substituted C.sub.2 -C.sub.20 straight chain alkenyl, an unsubstituted or substituted C.sub.3 -C.sub.20 branched chain alkenyl, a group of formula, ##STR2## a group of formula, ##STR3## a group of formula R.sup.4 --SO.sub.2 --, or a group of formula R.sup.5 --O--N.dbd.N(O)--. The compounds are potent nitric oxide releasing compounds.

Abstract: A method for the treatment of mammalian tissue injured or at risk of injury during sepsis or shock including the administration to a mammal a diazeniumdiolate which releases a therapeutically effective amount of nitric oxide sufficient to protect the tissue from sepsis- or shock-induced injury.

Abstract: A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N.sub.2 O.sub.2.sup.- functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.