Abstract: There is provided a method for the prevention and/or treatment of hypotension associated with hemodialysis, which method includes administering to a subject in need thereof an effective amount of at least one physiologically compatible compound which, in combination with iron, binds nitric oxide. There is further provided a method for identifying hemodialysis subjects for whom treatment with an effective amount of at least one physiologically compatible compound which, in combination with iron, binds nitric oxide is indicated. The method includes monitoring the subject's nitric oxide levels, and selecting those subjects having elevated nitric oxide levels for treatment with an effective amount of at least one physiologically compatible compound which, in combination with iron, binds nitric oxide, wherein the effective amount is sufficient to maintain the subject's nitric oxide levels within an acceptable range.

Abstract: In accordance with the present invention, there are provided novel chemical entities which have multiple utilities, e.g., as prodrugs of NSAIDs; as dual inhibitors of cyclooxygenase (COX) and 5-lipoxygenase (5-LO); as anticancer agents (through promoting apoptosis and/or inhibiting the matrix metalloproteinases (MMPs)); as anti-diabetics; and the like. Invention compounds comprise a non-steroidal anti-inflammatory agent (NSAID), covalently linked to a hydroxamate. Invention compounds are useful alone or in combination with one or more additional pharmacologically active agents, and can be used for a variety of applications, such as, for example, treating inflammation and inflammation-related conditions; reducing the side effects associated with administration of anti-inflammatory agents; promoting apoptosis; inhibiting matrix metalloproteinases; as anti-diabetic agents; and the like.

Abstract: In accordance with the present invention, there are provided conjugates of dithiocarbamates “DC”) and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein.

Abstract: In accordance with the present invention, there are provided modified forms of nonsteroidal anti-inflamamatory drugs (NSAIDs). Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

Abstract: In accordance with the present invention, there is provided a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. Thus, in accordance with the present invention, dithiocarbamates are linked to the surface of a non-immunogenic, non-targeting macromolecule other than an antibody (e.g., albumin protein) either by using cross-linking reagents or by nonspecific binding to produce polydithiocarbamate-macromolecule-containing compositions, which represent a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. In accordance with another aspect of the present invention, combinational therapeutic methods have been developed for the in vivo inactivation or inhibition of formation (either directly or indirectly) of species which induce the expression of inducible nitric oxide synthase, as well as reducing nitric oxide levels produced as a result of .NO synthase expression.

Abstract: The present invention provides novel combinations of dithiocarbamate disulfide dimers with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with a thiazolidinedione for the treatment of diabetes. In another embodiment, In another embodiment, invention combinations further comprise additional active agents such as, for example, metformin, insulin, sulfonylureas, and the like. In another embodiment, the present invention relates to compositions and formulations useful in such therapeutic methods.

Abstract: In accordance with the present invention, there are provided novel chemical entities which have multiple utilities, e.g., as prodrugs of NSAIDs; as dual inhibitors of cyclooxygenase (COX) and 5-lipoxygenase (5-LO); as anticancer agents (through promoting apoptosis and/or inhibiting the matrix metalloproteinases (MMPs)), and the like. Invention compounds comprise a non-steroidal anti-inflammatory agent (NSAID), covalently linked to a hydroxamate. Invention compounds are useful for a variety of applications, such as, for example, treating inflammation and inflammation-related conditions; reducing the side effects associated with administration of anti-inflammatory agents; promoting apoptosis; inhibiting matrix metalloproteinases; and the like.

Abstract: In accordance with the present invention, there is provided a new class of compounds, i.e., mono(dithio)carbamate esters of piperazine and analogs thereof, with or without substituents. Also provided are methods for the preparation of invention compounds and the pharmaceutical use thereof in the treatment of a variety of pathological conditions, especially for the treatment of cancers. A lead compound has shown good anticancer activity with low toxicity.

Abstract: The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

Abstract: Nitric oxide scavengers, such as dithiocarbamate-containing compounds, are used to reduce side effects caused by therapeutic administration of nitric oxide sources by administering the nitric oxide scavenger(s) to the subject after the therapeutic effect of the nitric oxide source has been achieved. For example, the nitric oxide source can be coadministered with the nitric oxide scavenger, with the latter formulated in a time release vehicle selected to delay release of the scavenger for a period of time sufficient to ensure that the therapeutic goal of the nitric oxide source has been achieved before release of the scavenger. Formulations and kits, including a bubble pack with pairwise arrangement of unit doses of a desired nitric oxide source and nitric oxide scavenger, are also provided.

Abstract: The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

Abstract: In accordance with the present invention, there are provided conjugates of nitric oxide scavengers (e.g., dithiocarbamates, or “DC”) and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein. In addition, invention conjugates are more effective than unmodified pharmacologically active agents because cells and tissues contacted by the pharmacologically active agent(s) are protected from the potentially damaging effects of nitric oxide overproduction induced thereby as a result of the co-production of nitric oxide scavenger (e.g., dithiocarbamate), in addition to free pharmacologically active agent, when invention conjugate is cleaved.

Abstract: In accordance with the present invention, there are provided normal modified forms of nonsteroidal anti-inflamamatory drugs. Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

Abstract: In accordance with the present invention, there are provided compounds and pharmaceutical compositions useful for the selective inhibition of COX-2 in the presence of COX-1. As a result, invention compounds and compositions provide anti-inflammatory relief to a subject in need thereof while dramatically reducing the occurrence of side effects in the subject. Compounds contemplated for use in the practice of the present invention are substituted heterocyclic compounds containing amidinyl and imidazolyl groups.

Abstract: The preparation and use of a protected organic aldehyde is described wherein bioavailability of the orally administered therapeutic aldehyde is improved. The protected aldehyde is prepared by reacting the aldehyde with a protecting group, for example, condensing the aldehyde chemically with a thiazolidine-4-carboxylic acid. The improved bioavailability of such orally administered drugs increases the feasibility of delivering sufficient amounts of vanillin or other therapeutic organic aldehydes in vivo to prevent sickling in sickle cell anemia. Combination therapy is also described wherein a protected organic aldehyde is administered to a subject in treatment of sickle cell anemia in conjunction with one or more other drugs, such as pain killers, used in treatment of the symptoms of sickle cell anemia or sickle cell disease.

Abstract: The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

Abstract: In accordance with the present invention, there are provided modified forms of nonsteroidal anti-inflammatory drugs (NSAIDs). Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

Abstract: In accordance with the present invention, there are provided conjugates of nitric oxide scavengers (e.g., dithiocarbamates, or “DC”) and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein. In addition, invention conjugates are more effective than unmodified pharmacologically active agents because cells and tissues contacted by the pharmacologically active agent(s) are protected from the potentially damaging effects of nitric oxide overproduction induced thereby as a result of the co-production of nitric oxide scavenger (e.g., dithiocarbamate), in addition to free pharmacologically active agent, when invention conjugate is cleaved.

Abstract: The preparation and use of a protected organic aldehyde is described wherein bioavailability of the orally administered therapeutic aldehyde is improved. The protected aldehyde is prepared by reacting the aldehyde with a protecting group, for example, condensing the aldehyde chemically with a thiazolidine-4-carboxylic acid. The improved bioavailability of such orally administered drugs increases the feasibility of delivering sufficient amounts of vanillin or other therapeutic organic aldehydes in vivo to prevent sickling in sickle cell anemia. Combination therapy is also described wherein a protected organic aldehyde is administered to a subject in treatment of sickle cell anemia in conjunction with one or more other drugs, such as pain killers, used in treatment of the symptoms of sickle cell anemia or sickle cell disease.

Abstract: In accordance with the present invention, there are provided normal modified forms of nonsteroidal anti-inflammatory drugs. Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.