William E Ballinger

Publications (2)7.8 Total impact

• Source

  Available from: 144.206.159.178

  Article: SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711.

  Margaret Y Chu-Moyer, William E Ballinger, David A Beebe, James B Coutcher, Wesley W Day, Jiancheng Li, Peter J Oates, R Matthew Weekly
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  ABSTRACT: SAR studies on the stereoisomers of CP-470,711 suggested that in vivo epimerization was taking place in rats. Further metabolism studies revealed that no epimerization was occurring in dogs, and that no epimerization was expected in humans. A mechanism for the in vivo epimerization is proposed involving an oxidation-reduction pathway of the secondary benzylic alcohol, in contrast to an acid/base-promoted epimerization of the same center during chemical synthesis.
  Bioorganic & Medicinal Chemistry Letters 07/2002; 12(11):1477-80. · 2.55 Impact Factor
• Article: Orally-effective, long-acting sorbitol dehydrogenase inhibitors: synthesis, structure-activity relationships, and in vivo evaluations of novel heterocycle-substituted piperazino-pyrimidines.

  Margaret Y Chu-Moyer, William E Ballinger, David A Beebe, Richard Berger, James B Coutcher, Wesley W Day, Jiancheng Li, Banavara L Mylari, Peter J Oates, R Matthew Weekly
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  ABSTRACT: Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED(90) < or = 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED(90) values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.
  Journal of Medicinal Chemistry 01/2002; 45(2):511-28. · 5.25 Impact Factor