Synthesis and Evaluation of N-acyl-2-(5-Fluorouracil-1-yl)-d,l-Glycine as a Colon-Specific Prodrug of 5-Fluorouracil

Synthesis and Evaluation of N-Nicotinoyl-2-{2-(2-Methyl-5-Nitroimidazol-1-yl)Ethyloxy}-D,L-Glycine as a Colon-Specific Prodrug of Metronidazole

“…We previously reported that N ‐acyl‐2‐acetoxy‐ D , L ‐glycine acts as a colon‐specific chemical drug delivery system for an anticancer agent, 5‐fluorouracil 17. Our data in this report indicated that the colon‐specific chemical drug delivery system also holds good for MTZ, thus bestowing colon targetability on MTZ.…”

“…In our previous paper, N ‐acyl‐2‐acetoxy‐ D , L ‐glycine was developed as a colon‐specific chemical drug‐delivery system, where the 2‐acetoxy group is easily substituted with a drug with a nucleophile to yield N ‐acyl‐2‐substituted‐ D , L ‐glycine 17, 21. We applied the delivery system to MTZ, a drug of choice for luminal amoebiasis.…”

“…In fact, a couple of reports on colonic delivery of MTZ using pharmaceutical approach have been published 14–16. In our previous report, we designed N ‐nicotinoyl‐2‐(5‐fuorouracil‐1‐yl)‐ D , L ‐glycine (NFG) as a colon‐specific prodrug of 5‐fuorouracil (5‐FU) and demonstrated that the prodrug was (bio)chemically stable in the upper intestinal condition and liberated 5‐FU when NFG was incubated with the large intestinal contents 17. In the present study, MTZ was coupled to N ‐nicotinoyl‐(2‐acetoxy)‐ D , L ‐glycine, the colon‐specific carrier of 5‐FU, to prepare N ‐nicotinoyl‐2‐{2‐(2‐methyl‐5‐nitroimidazol‐1‐yl)ethyloxy}‐ D , L ‐glycine (NMG).…”

Synthesis and Bioevaluation of 5-Fluorouracil Derivatives

“…To tackle these problems, numerous modifications of the 5-Fu structure have been performed. Thus, a series of 5-Fu prodrugs in which 5-Fu is attached to amino acids, peptides, phospholipids, and polymers have been reported [3][4][5][6][7]. These N-1 and/or N-3 substituted derivatives have exhibited improved pharmacological and pharmacokinetic properties, including increased bioactivity, selectivity, metabolic stability, absorption and lower toxicity.…”

5-Fluorouracil derivatives: a patent review (2012 – 2014)

“…These prodrugs are activated by a biological mediator only when get in specific cells or tissues [4]. 5-FU modifications include conjugation with peptides, amino acids, phospholipids and polymers [5][6][7][8][9]. Among 5-FU prodrugs tegafur, carmofur and floxuridine have already proven their clinical efficacy with low toxicity and increased selectivity and metabolic stability [10].…”