Sodium glucose co-transporter 2 (SGLT2) inhibitors: novel antidiabetic agents

Expert Opinion on Therapeutic Patents
William N Washburn

Abstract

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. 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. 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.

References

Dec 30, 2004·Diabetes/metabolism Research and Reviews·Joel R L EhrenkranzJesse Roth
Jan 16, 2007·Journal of Internal Medicine·E M WrightD F Loo
Aug 19, 2008·Bioorganic & Medicinal Chemistry Letters·Bruce A EllsworthWilliam N Washburn
Jan 8, 2009·Diabetes, Obesity & Metabolism·Iskandar Idris, Richard Donnelly
Oct 27, 2009·Expert Opinion on Therapeutic Patents·William N Washburn
Jun 16, 2010·Diabetic Medicine : a Journal of the British Diabetic Association·J E Gerich
Jan 8, 2011·Trends in Pharmacological Sciences·Clifford J Bailey
Mar 5, 2011·Kidney International. Supplement·Amanda Mather, Carol Pollock
Mar 5, 2011·Kidney International. Supplement·Masayuki Isaji
Mar 5, 2011·Kidney International. Supplement·James F List, Jean M Whaley
Mar 5, 2011·Kidney International. Supplement·Joaquim CaladoJosé Rueff
Aug 17, 2011·Nephron. Physiology·Carlos G Musso, Dimitrios G Oreopoulos
Dec 1, 2011·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Jian ChenJohn N Feder

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Citations

Dec 17, 2015·Expert Opinion on Therapeutic Patents·Marion Donnier-Maréchal, Sébastien Vidal
Jun 1, 2015·Bioorganic & Medicinal Chemistry Letters·Yuyang DingWenhui Hu
Oct 22, 2013·Natural Product Reports·Armin Bauer, Mark Brönstrup
Jun 6, 2014·ACS Medicinal Chemistry Letters·Sumihiro NomuraMinoru Tsuda-Tsukimoto
Apr 27, 2019·Expert Opinion on Therapeutic Patents·Jyotsana Pandey, Akhilesh K Tamrakar

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