title: Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: Pyridazinylmethylphenyl glucoside congeners.
abstract: 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.
authors.affiliation: Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Junwon
authors.initials: J
authors.lastname: Lee
authors.forename: Suk Youn
authors.initials: SY
authors.lastname: Kang
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Son
authors.forename: Myung Eun
authors.initials: ME
authors.lastname: Jung
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Kwang-Seop
authors.initials: KS
authors.lastname: Song
authors.forename: MinWoo
authors.initials: M
authors.lastname: Lee
authors.forename: Ho-Kyun
authors.initials: HK
authors.lastname: Han
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Kim
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
mesh_terms: 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
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors