2. Academic Validation
  3. C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications including C-5 spirocyclization

C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications including C-5 spirocyclization

  • Bioorg Med Chem Lett. 2010 Mar 1;20(5):1569-72. doi: 10.1016/j.bmcl.2010.01.075.
Ralph P Robinson 1,  Vincent Mascitti,  Carine M Boustany-Kari,  Christopher L Carr,  Patrick M Foley,  Emi Kimoto,  Michael T Leininger,  Andre Lowe,  Michelle K Klenotic,  James I Macdonald,  Robert J Maguire,  Victoria M Masterson,  Tristan S Maurer,  Zhuang Miao,  Jigna D Patel,  Cathy Préville,  Matthew R Reese,  Li She,  Claire M Steppan,  Benjamin A Thuma,  Tong Zhu
Affiliations

Affiliation

  • 1 Pfizer Global Research & Development, Groton Laboratories Eastern Point Rd, Groton, CT 06340, United States. ralph.p.robinson@pfizer.com
PMID: 20149653 DOI: 10.1016/j.bmcl.2010.01.075
Abstract

Modifications to the sugar portion of C-aryl glycoside sodium glucose transporter 2 (SGLT2) inhibitors were explored, including systematic deletion and modification of each of the glycoside hydroxyl groups. Based on results showing activity to be quite tolerant of structural change at the C-5 position, a series of novel C-5 spiro analogues was prepared. Some of these analogues exhibit low nanomolar potency versus SGLT2 and promote urinary glucose excretion (UGE) in rats. However, due to sub-optimal pharmacokinetic parameters (in particular half-life), predicted human doses did not meet criteria for further advancement.

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