Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: Pyridazinylmethylphenyl glucoside congeners.
Novel C-aryl glucoside SGLT2 inhibitors containing pyridazine motif were designed and synthesized for biological evaluation. Among the compounds tested, pyridazine containing methylthio moiety 22l or thiadiazole ring 22ah showed the best in vitro inhibitory activities in this series (IC(50)=13.4, 11.4nM, respectively) against SGLT2 to date. Subsequently, compound 22l exhibited reasonable urinary glucose excretion and glucosuria in normal SD rats, thereby demonstrating that this pyridazine series possesses both in vitro SGLT2 inhibition and in vivo efficacy, albeit to a lower degree.
Kim
Min Ju
MJ
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Lee
Junwon
J
Kang
Suk Youn
SY
Lee
Sung-Han
SH
Son
Eun-Jung
EJ
Jung
Myung Eun
ME
Lee
Suk Ho
SH
Song
Kwang-Seop
KS
Lee
MinWoo
M
Han
Ho-Kyun
HK
Kim
Jeongmin
J
Lee
Jinhwa
J
D000818:Animals; D005960:Glucosides / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D005960:Glucosides; D007004:Hypoglycemic Agents; C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors