Biphenylylacetic acid

Minami, K., Hirayama, F., and Uekama, K., Colon-specific drug delivery based on a cyclodextrin prodrug release behavior of biphenylylacetic acid from its cyclodextrin conjugates in rat intestinal tracts after oral administration, J. Pharm. Sci., 87 715-720 (1998). 

Juaristi, E. Martinez-Richa, A. Garcia-Rivera, A. Cruz-Sanchez, J. S. Use of 4-biphenylyl-mefhanol, 4-biphenylylacetic acid, and 4-biphenylcarboxylic add/triphenylmethane as indicators in the titration of lithium alkyls. Study of the dianion of 4-biphenylylmethanol. /. Org. Chem. 1983, 48, 2603-2606. 

Arima, H., Kondo, T., Me, T. Use of water-soluble (3-cyclodextrin derivatives as carriers of anti-inflammatory drug biphenylylacetic acid in rectal delivery. Yakugaku. Zasshi 1992, 112, 65-72. 

Arima, H., Adachi, H., Irie, T., Uekama, K. Improved drug delivery through the skin by hydrophilic p-cyclodextrins enhancement of anti-inflammatory effect of 4-biphenylylacetic acid in rats. Drug Invest. 1990, 2,155-161. 

Uekama, K., Maeda, T., Arima, H. et al. Possible utility of p-cyclodextrin complexation in the preparation of biphenylylacetic acid suppository. Yakugaku. Zasshi 1986, 106, 1126-1130. 

Hirayama, E, Minami, K. In vitro evaluation of biphenylylacetic acid 3-cyclodextrin conjugate as colon-targeting prodrug drug release behavior in rat biological fluids. J. Pharm. Pharmacol. 1996, 48, 27-31. 

Reagents and standards. All the chemicals used were of analytical reagent grade and were tested for purity in blank runs. Ketodase was obtained from Warner-Chilcott, Morris Plains, N.J., U.S.A. Biphenylylacetic acid was synthesized from biphenyl and acetic chloride by a Friedel-Crafts reaction followed by a Willgerodt-Kindler reaction. -Hydroxybiphenylylacetic acid was prepared in a similar way from p-methoxybiphenyl. The amino acid conjugates were obtained by reaction of biphenylylacetyl chloride and -acetoxybiphenylylacetyl chloride with the appropriate amino acid. 

The mass spectrum of the fraction with R 0.40 is shown in Fig. The major fragmentation corresponds to loss of 45 amu from the M suggesting loss of a -COoH group to give the relatively stable phenyltropylium ion at my el 167. On this basis the compound was assigned the structure of biphenylylacetic acid (BPA) and this was confirmed by comparison with an authentic sample of BPA. 

In the stomach and in the intestine (Table 9) most of the difenpiramide is not metabolized. The recovery of the metabolites in the stomach is 42.66% the amount of a-aminopyridine found is always a little less than the sum of the amount of biphenyly lace tic acid and p -hydroxybiphenylylacetic acid. The total recovery of difenpiramide biphenylylacetic acid, -hydroxybiphenylylacetic acid and a-aminopyridine, in urine, bile and stomach of rat is about... 

In conclusion difenpiramide is hydrolyzed in the body to biphenylylacetic acid and a-aminopyridine. Biphenyly lacetic acid is metabolized to -hydroxybiphenylylacetic acid by hydroxylation of the biphenyl group in the p-position. Biphenylylacetic acid is pharmacologically active, while -hydroxybiphenylylacetic acid is inactive. An amount of these two acids made water soluble by conjugation (mainly with glucuronic acid, in part with amino acids) are excreted in the urine. Biphenylylacetic acid is found in... 

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