RESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/síntese química , Hipoglicemiantes/síntese química , Rim/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose , Administração Oral , Animais , Compostos Benzidrílicos , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Ratos , Transportador 2 de Glucose-Sódio , EstereoisomerismoRESUMO
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.
Assuntos
Androgênios , Músculos/efeitos dos fármacos , Músculos/metabolismo , Oxazóis/química , Oxazóis/farmacologia , Animais , Cristalografia por Raios X , Humanos , Concentração de Íons de Hidrogênio , Masculino , Modelos Moleculares , Conformação Molecular , Próstata/efeitos dos fármacos , Próstata/metabolismo , Ratos , Especificidade por SubstratoRESUMO
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.