Thiazolidinediones (TZDs) are a group of structurally related peroxisome proliferator-activated receptor γ (PPARγ) agonists with antidiabetic actions in vivo.1,2 Rosiglitazone (BRL 49653) is a prototypical TZD and has served as a reference compound for this class.3 Rosiglitazone is a potent and selective PPARγ ligand. It binds to the PPARγ ligand-binding domain with a Kd of 43 nM.3 It activates luciferase-based expression constructs PPARγ1 and PPARγ2 with EC50 values of approximately 30 nM and 100 nM, respectively.3 Rosiglitazone is active in vivo as a antidiabetic agent in the ob/ob mouse model, and has been used as an oral hypoglycemic agent in the treatment of Type II diabetes in humans for many years.
1
Willson, T.M., Cobb, J.E., Cowan, D.J., et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem39665-668(1996).
2
Cantello, B.C.C., Cawthorne, M.A., Cottam, G.P., et al. [[ω-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents. J Med Chem373977-3985(1994).
3
Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-acivated receptor γ (PPARγ). J Biol Chem27012953-12956(1995).
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O=C1NC(=O)C(S1)Cc1ccc(OCCN(C)c2ccccn2)cc1
Background Reading
Willson, T.M., Cobb, J.E., Cowan, D.J., et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem39665-668(1996).
Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-acivated receptor γ (PPARγ). J Biol Chem27012953-12956(1995).
Cantello, B.C.C., Cawthorne, M.A., Cottam, G.P., et al. [[ω-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents. J Med Chem373977-3985(1994).
Rosiglitazone is available in the following screening
library: