title: SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711.
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.
authors.affiliation: 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
authors.forename: Margaret Y
authors.initials: MY
authors.lastname: Chu-Moyer
authors.forename: William E
authors.initials: WE
authors.lastname: Ballinger
authors.forename: David A
authors.initials: DA
authors.lastname: Beebe
authors.forename: James B
authors.initials: JB
authors.lastname: Coutcher
authors.forename: Wesley W
authors.initials: WW
authors.lastname: Day
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Li
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oates
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Weekly
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D007064:L-Iditol 2-Dehydrogenase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism*; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: C467608:CP-470711; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D007064:L-Iditol 2-Dehydrogenase