The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents wherein the drug or therapeutic agents contain at least one carboxylic acid group. The invention also relates to processes for the preparation of these nitric oxide releasing prodrugs, to pharmaceutical compositions containing them and to methods of using these produgs.

The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents wherein the drug or therapeutic agents contain at least one carboxylic acid group. The invention also relates to processes for the preparation of these nitric oxide releasing prodrugs, to pharmaceutical compositions containing them and to methods of using these produgs.

Disclosed is a process for the synthesis of mono- and bis-nitrosylated propanediols, as well as compositions and pharmaceutical formulations that includes the compounds. The process proceeds by reacting a corresponding propanediol that is not nitrosylated with a source of nitrite, optionally in the presence of a suitable acid. When the source of nitrite is an organic nitrite, reacting step is performed in a suitable organic solvent, and when the source of nitrite is an inorganic nitrite, the reacting step is performed in a bi-phasic solvent mixture comprising an aqueous phase and a non-aqueous phase. Also disclosed are methods of treating a condition wherein administration of nitric oxide (NO) has a beneficial effect by administering said compounds, compositions or formulations.

Disclosed is a process for the synthesis of mono- and bis-nitrosylated propanediols, as well as compositions and pharmaceutical formulations that includes the compounds. The process proceeds by reacting a corresponding propanediol that is not nitrosylated with a source of nitrite, optionally in the presence of a suitable acid. When the source of nitrite is an organic nitrite, reacting step is performed in a suitable organic solvent, and when the source of nitrite is an inorganic nitrite, the reacting step is performed in a bi-phasic solvent mixture comprising an aqueous phase and a non-aqueous phase. Also disclosed are methods of treating a condition wherein administration of nitric oxide (NO) has a beneficial effect by administering said compounds, compositions or formulations.

Disclosed is a process for the synthesis of mono- and bis-nitrosylated propanediols, as well as compositions and pharmaceutical formulations that includes the compounds. The process proceeds by reacting a corresponding propanediol that is not nitrosylated with a source of nitrite, optionally in the presence of a suitable acid. When the source of nitrite is an organic nitrite, reacting step is performed in a suitable organic solvent, and when the source of nitrite is an inorganic nitrite, the reacting step is performed in a bi-phasic solvent mixture comprising an aqueous phase and a non-aqueous phase. Also disclosed are methods of treating a condition wherein administration of nitric oxide (NO) has a beneficial effect by administering said compounds, compositions or formulations.

An elegant process for the synthesis of 2-nitratoethyl acrylate is a single reactive step. A 2-hydroxyethyl acrylate having only one hydroxyl group is nitrated in a 1:1 volumetric mixture of nitric acid and sulfuric acid therein forming 2-nitratoethyl acrylate. The 2-nitratoethyl acrylate is minimally soluble in a quenched cold acid water mixture, which enables relatively easy isolation of about 96% purity 2-nitratoethyl acrylate at a yield of about 85%.

An elegant process for the synthesis of 2-nitratoethyl acrylate is a single reactive step. A 2-hydroxyethyl acrylate having only one hydroxyl group is nitrated in a 1:1 volumetric mixture of nitric acid and sulfuric acid therein forming 2-nitratoethyl acrylate. The 2-nitratoethyl acrylate is minimally soluble in a quenched cold acid water mixture, which enables relatively easy isolation of about 96% purity 2-nitratoethyl acrylate at a yield of about 85%.

A method for producing an alkyl nitrite by bringing an aqueous solution containing nitric acid and an alkanol into contact with a gas including nitrogen monoxide and thereby producing an alkyl nitrite, in which the reaction temperature is 60 C. to 100 C., is provided.

A method for producing an alkyl nitrite by bringing an aqueous solution containing nitric acid and an alkanol into contact with a gas including nitrogen monoxide and thereby producing an alkyl nitrite, in which the reaction temperature is 60 C. to 100 C., is provided.

The invention discloses a method for the continuous preparation of n-butyl nitrite with a low content of n-butanol comprising the reaction of n-butanol, an acid and NaNO.sub.2 in a continuous way, in which the n-butanol, an acid and NaNO.sub.2 are mixed in a mixing device which provides for a pressure drop of at least 1 bar; the acid is selected from the group consisting of HCI, H.sub.2SO.sub.4, formic acid, methanesulfonic acid, and mixtures thereof; and the amount of HCI is at least 1.02 molar equivalent based on the molar amount of n-butanol.