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ID: ALA2413069
Journal: Bioorg Med Chem
Title: C-Glucosides with heteroaryl thiophene as novel sodium-dependent glucose cotransporter 2 inhibitors.
Authors: Koga Y, Sakamaki S, Hongu M, Kawanishi E, Sakamoto T, Yamamoto Y, Kimata H, Nakayama K, Kuriyama C, Matsushita Y, Ueta K, Tsuda-Tsukimoto M, Nomura S.
Abstract: Canagliflozin (1), a novel inhibitor for sodium-dependent glucose cotransporter 2 (SGLT2), has been developed for the treatment of type 2 diabetes. To investigate the effect of replacement of the phenyl ring in 1 with heteroaromatics, C-glucosides 2 were designed, synthesized, and evaluated for their inhibitory activities against SGLT2. Of these, 3-pyridyl, 2-pyrimidyl or 5-membered heteroaryl substituted derivatives showed highly potent inhibitory activity against SGLT2, while 5-pyrimidyl substitution was associated with slightly reduced activity. In particular, 2g (TA-3404) had remarkable anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.
CiteXplore: 23809172