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Mylari, B.L. et al.

Mylari, Oates, Zembrowski, Beebe, Conn, Coutcher, O'Gorman, Linhares, Withbroe,

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.

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.[1]

References

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. Mylari, B.L., Oates, P.J., Zembrowski, W.J., Beebe, D.A., Conn, E.L., Coutcher, J.B., O'Gorman, M.T., Linhares, M.C., Withbroe, G.J. J. Med. Chem. (2002) [Pubmed]

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