title: Sodium glucose co-transporter 2 (SGLT2) inhibitors: novel antidiabetic agents.
abstract: BACKGROUND
  Maintenance of glucose homeostasis in healthy individuals involves SGLT2 (sodium glucose co-transporter 2)-mediated recovery of glucose from the glomerular filtrate which otherwise would be excreted in urine. Clinical studies indicate that SGLT2 inhibitors provide an insulin-independent means to reduce the hyperglycemia that is the hallmark of type 2 diabetes mellitus (T2DM) with minimal risk of hypoglycemia.
  
  
  METHODS
  The pharmacophore common to the SGLT2 inhibitors currently in development is a diarylmethane C-glucoside which is discussed in this review. The focus is how this pharmacophore was further modified as inferred from the patents publishing from 2009 to 2011. The emphasis is on the strategy that each group employed to circumvent the constraints imposed by prior art and how the resulting SGLT2 potency and selectivity versus SGLT1 compared with that of the lead clinical compound dapagliflozin.
  
  
  CONCLUSIONS
  SGLT2 inhibitors offer a new fundamentally different approach for treatment of diabetes. To date, the clinical results suggest that for non-renally impaired patients this class of inhibitors could be safely used at any stage of T2DM either alone or in combination with other marketed antidiabetic medications.
authors.affiliation: Metabolic Diseases Chemistry, Research and Development, Bristol-Myers Squibb Co., P.O. Box 5400, Princeton, NJ 08543, USA. william.washburn@bms.com
authors.forename: William N
authors.initials: WN
authors.lastname: Washburn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007880:Legislation, Drug; D015394:Molecular Structure; D010330:Patents as Topic; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors