A sorbitol dehydrogenase inhibitor of exceptional in vivo potency with a long duration of action: 1-(R)-[4-[4-(4,6-dimethyl[1,3,5]triazin-2-yl)- 2R,6S-dimethylpiperazin-1-yl]pyrimidin-2- yl]ethanol

  • J Med Chem. 2002 Sep 26;45(20):4398-401. doi: 10.1021/jm020288y.
Banavara L Mylari  1 ,  Peter J Oates ,  William J Zembrowski ,  David A Beebe ,  Edward L Conn ,  James B Coutcher ,  Melissa T O'Gorman ,  Michael C Linhares ,  Gregory J Withbroe
Affiliations
  • 1. Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut 06340, USA. [email protected]
PMID: 12238919 DOI: 10.1021/jm020288y
Abstract

We report here a novel sorbitol dehydrogenase inhibitor, 16, that shows very high oral potency (50 microg/kg) in normalizing elevated fructose levels in the sciatic nerve of chronically diabetic rats and sustained duration of action (>24 h). Furthermore, 16 shows attractive pharmaceutical properties, including good solubility in simulated human gastric fluid, excellent Caco-2 Papp, moderate lipophilicity, and metabolic stability for achieving good oral absorption and long duration of action.

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