SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor,CP-470,711 |
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| Authors: | Chu-Moyer Margaret Y Ballinger William E Beebe David A Coutcher James B Day Wesley W Li Jiancheng Oates Peter J Weekly R Matthew |
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| Institution: | Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton Laboratories MS8220-3095, Eastern Point Road, CT 06340, USA. margaret_y_chu-moyer@groton.pfizer.com |
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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. |
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