Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: 1,3,4-Thiadiazolylmethylphenyl glucoside congeners.
Novel C-aryl glucoside SGLT2 inhibitors containing 1,3,4-thiadiazole moieties were designed and synthesized. Among the compounds tested, biaryl-type compounds containing pyrazine 59, 2-furan 61, and 3-thiophene 71 showed the best in vitro inhibitory activities to date (IC(50) = 3.51-7.03 nM) against SGLT2. A selected compound 61, demonstrated reasonable blood glucose-lowering effects, indicating that the information obtained from the SAR studies in this 1,3,4-thiadiazolylmethylphenyl glucoside series might help to design more active SGLT2 inhibitors that are structurally related.
Lee
Junwon
J
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Lee
Sung-Han
SH
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Seo
Hee Jeong
HJ
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Son
Eun-Jung
EJ
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Lee
Suk Ho
SH
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Jung
Myung Eun
ME
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Lee
MinWoo
M
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Han
Ho-Kyun
HK
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Kim
Jeongmin
J
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Kang
Jahyo
J
Department of Chemistry, Sogang University, 1 Shinsu-Dong, Mapo-Gu, Seoul 121-742, Republic of Korea.
Lee
Jinhwa
J
Central Research Laboratories, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy; D015195:Drug Design; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C549693:1,3,4-thiadiazolylmethylphenyl glucoside; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013830:Thiadiazoles