RESUMO
A series of indole-O-glucosides and C-glucosides was synthesized and evaluated in SGLT1 and SGLT2 cell-based functional assays. Compounds 2a and 2o were identified as potent SGLT2 inhibitors and screened in ZDF rats.
Assuntos
Glucosídeos/química , Glucosídeos/farmacologia , Indóis/química , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Diabetes Mellitus Experimental/urina , Glucose/metabolismo , Glucosídeos/síntese química , Estrutura Molecular , Ratos , Ratos Zucker , Transportador 1 de Glucose-Sódio/antagonistas & inibidoresRESUMO
A series of benzo-fused heteroaryl-O-glucosides was synthesized and evaluated in SGLT1 and 2 cell-based functional assays. Indole-O-glucoside 10a and benzimidazole-O-glucoside 18 exhibited potent in vitro SGLT2 inhibitory activity.
Assuntos
Glucosídeos/química , Glucosídeos/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose , Glucosídeos/síntese química , Humanos , Estrutura MolecularRESUMO
A series of glucose conjugates was synthesized and tested for inhibition of SGLT1 and SGLT2. The core structure was derived from compound 1a. Modification of the benzofuran moiety and 4'-substituent of the phenyl ring in compound 1a improved selectivity at SGLT2. Select compounds were compared to 1a in metabolic stability and in vivo efficacy studies.
