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

  • Bioorg Med Chem Lett. 2002 Jun 3;12(11):1477-80. doi: 10.1016/s0960-894x(02)00208-1.
Margaret Y Chu-Moyer  1 ,  William E Ballinger ,  David A Beebe ,  James B Coutcher ,  Wesley W Day ,  Jiancheng Li ,  Peter J Oates ,  R Matthew Weekly
Affiliations
  • 1. Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton Laboratories MS8220-3095, Eastern Point Road, CT 06340, USA. [email protected]
PMID: 12031323 DOI: 10.1016/s0960-894x(02)00208-1
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.

Products