4k26

Publication Abstract from PubMed

Racemic cis-1,1-dioxo-5,6-dihydro-[4,1,2]oxathiazine derivative 4a was isolated as an impurity in a sample of a hit from a HTS campaign on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). After separation by chiral chromatography the 4a-S, 8a-R enantiomer of compound 4a was identified as the true, potent enzyme inhibitor. The cocrystal structure of 4a with human and murine 11ss-HSD1 revealed the unique binding mode of the oxathiazine series. SAR elucidation and optimization in regard to metabolic stability led to monocyclic tetramethyloxathiazines as exemplified by compound 21g.

1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11ss-HSD1 inhibitors for the treatment of diabetes.,Bohme T, Engel CK, Farjot G, Gussregen S, Haack T, Tschank G, Ritter K Bioorg Med Chem Lett. 2013 Aug 15;23(16):4685-91. doi:, 10.1016/j.bmcl.2013.05.102. Epub 2013 Jun 11. PMID:23845218^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.