A process for preparation of the thioester of N-acetyl- cysteine

摘要

The thioester of N-acetyl-cysteine with p-isobutylphenyl- propionic acid shows simultaneous anti-inflammatory and mucolytic activity. It is prepared by the reaction of a reactive derivative of p-isobutylphenylpropionic acid and N-acetyl-cysteine at low temperature in a polar solvent. Salts with organic and inorganic bases, with basic amino acids and with basic antibiotics which have a macromolecular structure are stable and generally soluble in water, as a result of which the active ingredient according to the invention can be formulated for oral, parenteral, rectal and topical administration. This invention relates to a thioester of N-acetyl- cysteine propionyl glycine with p-isobutylphenylpropionic acid, which has the formula: and which has useful anti-inflammatory and mucolytic properties, and its pharmacologically acceptable non- toxic salts. The anti-inflammatory activity of p- isobutylphenylpropionic acid is known, and the disadvantages from the point of view of its therapeutic use are also known. The compound according to the invention, as such or converted into a salt with organic bases containing alkaline or alkaline earth ions, or with basic amino acids such as arginine and lysine, or with the nuclei of basic antibiotics such as erythromycin and propionyl erythromycin, demonstrate useful properties as they have anti-inflammatory and mucolytic activity at the same time. This invention also relates to processes for the preparation of the subject compound which are characterised in that a p-isobutylphenylpropionic acid halide and a derivative of N-acetyl-cysteine are caused to react in a medium which has an alkaline pH containing a polar solvent, preferably water or mixtures of water and dioxan, at low temperature, giving rise to a low melting point thioester which is an odourless pale yellow oil at ambient temperature. The reaction product as such is free from impurities and is used in the reaction to form the salt with the various bases mentioned above in order to obtain the corresponding salts, which are stable, water-soluble and easy to use in the pharmaceutical field.