4 - Aminosalicylic Acid Phenol Azo Derivatives Of Anti-ulcer Colitis Drug Synthesis

Ulcerative colitis(UC), are chronic inflammatory bowel diseases of unknown aetiology. 5-aminosalicylic acid (5-ASA) species, especially Sulfusalazine (SASP), had been using as the preferred medicine for the treatment of UC, Numerous clinical studies have shown that 4-aminosalicylic acid (4-ASA) is highly effective and safe in topical treatment of UC, but after oral administration, 4-ASA were rapidly absorbed in the upper intestinal tract, before it reaches to the colonic site. Therefore by modifying the structure of 4-ASA, we synthesized azo derivatives of 4-ASA.According to the evident curative effects of 4-ASA, this experiment adopt the prodrug principle of 5-ASA derivatives, and designed and conducted the synthesis of azo derivatives of 4-ASA. 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively. The resultant was hydrogenised to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with a set of carrier moleculers to get azo derivatives of 4-ASA. The azo derivatives were hydrolyzed under the alkaline condition to get the target products. Because the pathogenesis of UC may be related to the presence of excess free oxygen radicals in immunoreaction, we selected various substituted phenols, with different reducibility, to conjugate with 4-aminosalicylic acid, seven new azo derivatives of 4-aminosalicylic acid were successfully synthesized. The structures of the new derivatives of 4-ASA were characterized by melting point, TLC, MS, FT-IR, 1H-NMR and 13C-NMR spectra properties in details.