Pyrazole-O-glucosides as novel Na(+)-glucose cotransporter (SGLT) inhibitors.
O-glucuronides and O-glucosides of a series of pyrazoles analogues were synthesized and evaluated for their SGLT inhibitory activity in brush border membrane vehicles (BBMVs) of rat kidney. O-glucosides of certain pyrazole analogues inhibited the transport of [(14)C]-glucose in BBMVs, and induced glucosuria in Wistar rats by intravenous injection.
Ohsumi
Koji
K
Pharmaceutical Research Laboratories, Pharmaceutical Company, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-ku, 210-8681, Kawasaki, Japan. koji_ohsumi@ajinomoto.com
Matsueda
Hiroyuki
H
Hatanaka
Toshihiro
T
Hirama
Ryusuke
R
Umemura
Takashi
T
Oonuki
Akiko
A
Ishida
Nozomu
N
Kageyama
Yoko
Y
Maezono
Katsumi
K
Kondo
Nobuo
N
D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D006029:Glycosuria / Q000139:chemically induced / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D011720:Pyrazoles; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; C101725:WAY 123783; D005947:Glucose