Abstract
As a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA), 5-aminosalicyl-glycine (5-ASA-Gly) was prepared by a simple synthetic route in good yield. Apparent partition coefficients of 5-ASA-Gly were lower than those of 5-ASA, which determined in CHCl3/pH 6.8 buffer or n-octanol/pH 6.8 buffer system. Stability of 5-ASA-Gly by peptidases was investigated by incubation of 5-ASA-Gly with the homogenates of tissue and contents of stomach, proximal small intestine or distal small intestine of rats at 37°C. 5-ASA was not detected, indicating that the prodrug was stable in the upper intestine. The amount of 5-ASA liberated from incubation of the prodrug in cecal or colonic contents of rats was about 65% or 27% in 8 hrs, respectively, which indicated that the prodrug activation took place more readily in the rat cecum whose bacterial counts are high like human colon. Results fromin vitro experiments suggested 5-ASA-Gly as a promising candidate of a colon-specific prodrug of 5-ASA.
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Jung, Y.J., Lee, J.S., Kim, H.H. et al. Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid. Arch. Pharm. Res. 21, 174–178 (1998). https://doi.org/10.1007/BF02974024
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DOI: https://doi.org/10.1007/BF02974024