Citation: Shuo Zhang, Yu-Li Wang, Qun-Chao Wei, Wei-Ren Xu, Li-Da Tang, Gui-Long Zhao, Jian-Wu Wang. Design, synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors[J]. Chinese Chemical Letters, ;2013, 24(05): 429-432. shu

Design, synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors

1.
a School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China;
2.
b Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China

Corresponding author: Gui-Long Zhao, Jian-Wu Wang,
Received Date: 22 January 2013
Available Online: 11 March 2013

Seven cyclohexane-bearing C-glucoside derivatives (7, 9, 12, 13 and 17-19) were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, (1S)-1-deoxy-1-[4-methoxy-3-(trans-n-propylcyclohexyl)methylphenyl]-D-glucose (1). The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLT1 inhibition and urinary glucose excretion (UGE), respectively. Among the synthesized compounds 12, the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor (IC₅₀ = 1.4 nmol/L against hSGLT2; selectivity = 1576). Compound 12 was a potent SGLT2 inhibitor, which could induce more urinary glucose than 1 and dapagliflozin in UGE.
- Synthesis,
- C-Glucoside,
- SGLT2 inhibitor,
- Urinary glucose excretion,
- Cyclohexane-bearing
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