Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: 1,3,4-Thiadiazolylmethylphenyl glucoside congeners

作者：Lee Junwon; Lee Sung Han; Seo Hee Jeong; Son Eun Jung; Lee Suk Ho; Jung Myung Eun; Lee MinWoo; Han Ho Kyun; Kim Jeongmin; Kang Jahyo^*; Lee Jinhwa

来源：Bioorganic & Medicinal Chemistry, 2010, 18(6): 2178-2194.

DOI：10.1016/j.bmc.2010.01.073

• SGLT
• Dapagliflozin
• Thiadiazole
• Glucoside
• Diabetes

Novel C-aryl glucoside SGLT2 inhibitors containing 1,3,4-thiadiazole moieties were designed and synthesized. Among the compounds tested, biaryl-type compounds containing pyrazine 59, 2-furan 61, and 3-thiophene 71 showed the best in vitro inhibitory activities to date (IC50 = 3.51-7.03 nM) against SGLT2. A selected compound 61, demonstrated reasonable blood glucose-lowering effects, indicating that the information obtained from the SAR studies in this 1,3,4-thiadiazolylmethylphenyl glucoside series might help to design more active SGLT2 inhibitors that are structurally related.

• 出版日期2010-3-15