Novel L-xylose derivatives as selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes

Journal of Medicinal Chemistry

Volumn 52, Issue 20, 2009, Pages 6201-6204

  Goodwin, Nicole C ^a   Mabon, Ross ^a   Harrison, Bryce A ^a   Shadoan, Melanie K ^a   Almstead, Zheng Y ^a   Xie, Yiling ^a   Healy, Jason ^a   Buhring, Lindsey M ^a   DaCosta, Christopher M ^a   Bardenhagen, Jennifer ^a   Mseeh, Faika ^a   Liu, Qingyun ^a   Nouraldeen, Amr ^a   Wilson, Alan G E ^a   Kimball, S David ^a   Powell, David R ^a   Rawlins, David B ^a  

^a LEXICON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; DAPAGLIFLOZIN; GLUCOSE; O XYLOSIDE 7C; REMOGLIFOZIN; SERGLIFLOZIN; SODIUM GLUCOSE COTRANSPORTER 2; UNCLASSIFIED DRUG; XYLOSE DERIVATIVE;

ARTICLE; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; DRUG TOLERABILITY; GLUCOSE HOMEOSTASIS; GLUCOSE URINE LEVEL; HUMAN; IC 50; IN VITRO STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PREVALENCE; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

ANIMALS; DIABETES MELLITUS, TYPE 2; DRUG DISCOVERY; GLUCOSE; HUMANS; MICE; SODIUM-GLUCOSE TRANSPORTER 2; SUBSTRATE SPECIFICITY; XYLOSE;

EID: 70350075459     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900951n     Document Type: Article

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29. The published selectivity of dapagliflozin for hSGLT1/hSGLT2 is 1200-fold (see ref 19). However, in our assays, we observed a 169-fold selectivity for hSGLT2. See Supporting Information for further details on the experimental methods used in this report.
30. The full diastereoselective synthesis starting from commercially available L-xylose is provided in the Supporting Information.