Thiazolylmethyl ortho-substituted phenyl glucoside library as novel C-aryl glucoside SGLT2 inhibitors

Suk Ho Lee; Min Ju Kim; Sung-Han Lee; Jeongmin Kim; Hyun-Ju Park; Jinhwa Lee

doi:10.1016/j.ejmech.2011.03.052

Thiazolylmethyl ortho-substituted phenyl glucoside library as novel C-aryl glucoside SGLT2 inhibitors

Eur J Med Chem. 2011 Jul;46(7):2662-75. doi: 10.1016/j.ejmech.2011.03.052. Epub 2011 Apr 2.

Authors

Suk Ho Lee¹, Min Ju Kim, Sung-Han Lee, Jeongmin Kim, Hyun-Ju Park, Jinhwa Lee

Affiliation

¹ Green Cross Corporation Research Center, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.

PMID: 21514014
DOI: 10.1016/j.ejmech.2011.03.052

Abstract

In order to investigate SAR regarding proximal phenyl ring in novel C-aryl glucoside SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications on proximal phenyl ring was conducted. During a series of lead optimization efforts, ortho-allyloxyphenyl 10p or ortho-hydroxyphenyl 11a showed subnanomolar inhibitory activity against hSGLT2.

MeSH terms

Animals
Biological Transport / drug effects
CHO Cells
Carbon Radioisotopes
Cricetulus
Gene Expression
Glucosides / chemical synthesis*
Glucosides / pharmacology
Humans
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / pharmacology
Methylglucosides / metabolism
Recombinant Proteins / chemistry
Small Molecule Libraries / chemical synthesis*
Small Molecule Libraries / pharmacology
Sodium-Glucose Transporter 2 / chemistry
Sodium-Glucose Transporter 2 Inhibitors*
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / pharmacology

Substances

Carbon Radioisotopes
Glucosides
Hypoglycemic Agents
Methylglucosides
Recombinant Proteins
SLC5A2 protein, human
Small Molecule Libraries
Sodium-Glucose Transporter 2
Sodium-Glucose Transporter 2 Inhibitors
Thiazoles