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

  • Bioorg Med Chem. 2010 Mar 15;18(6):2178-2194. doi: 10.1016/j.bmc.2010.01.073.
Junwon Lee  1 ,  Sung-Han Lee  1 ,  Hee Jeong Seo  1 ,  Eun-Jung Son  1 ,  Suk Ho Lee  1 ,  Myung Eun Jung  1 ,  MinWoo Lee  1 ,  Ho-Kyun Han  1 ,  Jeongmin Kim  1 ,  Jahyo Kang  2 ,  Jinhwa Lee  1
Affiliations
  • 1. Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
  • 2. Department of Chemistry, Sogang University, 1 Shinsu-Dong, Mapo-Gu, Seoul 121-742, Republic of Korea.
PMID: 20181486 DOI: 10.1016/j.bmc.2010.01.073
Abstract

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 (IC(50) = 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.