RESUMEN
The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/síntesis química , Hipoglucemiantes/síntesis química , Riñón/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Administración Oral , Animales , Compuestos de Bencidrilo , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucósidos/química , Glucósidos/farmacología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Ratas , Transportador 2 de Sodio-Glucosa , EstereoisomerismoRESUMEN
A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.
Asunto(s)
Andrógenos , Músculos/efectos de los fármacos , Músculos/metabolismo , Oxazoles/química , Oxazoles/farmacología , Animales , Cristalografía por Rayos X , Humanos , Concentración de Iones de Hidrógeno , Masculino , Modelos Moleculares , Conformación Molecular , Próstata/efectos de los fármacos , Próstata/metabolismo , Ratas , Especificidad por SustratoRESUMEN
Replacement of the 3-oxo group of 2-chloro-4-[(7R,7aS)-7-hydroxy-1,3-dioxotetrahydro-1H-pyrrolo[1,2c]imidazol-2(3H)-yl]-3-methylbenzonitrile resulted in a sulfamide series of selective androgen receptor modulator (SARM) agonists.