An evaluation of US patent 2015065565 (A1) for a new class of SGLT2 inhibitors for treatment 1 of type II diabetes mellitus.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a growing and serious global health problem. Pharmacological inhibition of the sodium-glucose cotransporter-2 (SGLT2; SLC5A2) increases urinary glucose excretion, decreasing plasma glucose levels in an insulin-independent manner. Agents that inhibit SGLT2 have recently become available for clinical therapy of T2DM.


METHODS
The patent claims a new class of SGLT2 inhibitors: derivatives of dioxa-bicyclo[3.2.1]octane-2,3,4-triol (including ertugliflozin; PF-04971729). The invention describes the design, synthesis and pharmacological tests related to ertugliflozin, which could ultimately lead to efficacious therapy for T2DM alone or in combination with other anti-diabetic agents.


CONCLUSIONS
Ertugliflozin is likely to be of great clinical significance in the near future. Continued analysis of ertugliflozin derivatives to now validate safe and efficacious treatment of T2DM in a larger number of clinical subjects over an extended period is needed to further support clinical utility. Identification, and discussion, of likely contra-indications is also needed.
a Oregon Health & Science University, Otolaryngology, Oregon Hearing Research Center , 3181 SW Sam Jackson Park Road, Portland, USA steygerp@ohsu.edu.
Meiyan
M
Jiang
a Oregon Health & Science University, Otolaryngology, Oregon Hearing Research Center , 3181 SW Sam Jackson Park Road, Portland, USA steygerp@ohsu.edu.
Peter S
PS
Steyger
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D010330:Patents as Topic; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570288:ertugliflozin
PF-04971729; clinical therapy; diabetes; dioxa-bicyclo[3.2.1]octane-2,3,4-triol derivatives; ertugliflozin; inhibitors; sodium–glucose linked co-transporter; type 2 diabetes mellitus