TY - JOUR
T1 - Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase
AU - Zhang, Lei
AU - Li, Honglin
AU - Zhu, Qingzhang
AU - Liu, Jun
AU - Chen, Ling
AU - Leng, Ying
AU - Jiang, Hualiang
AU - Liu, Hong
N1 - Funding Information:
We gratefully acknowledge generous support from the National Natural Science Foundation of China (Grants 20372069 , 29725203 , 20803022 , and 20472094 ), the Basic Research Project for Talent Research Group from the Shanghai Science and Technology Commission, the Key Project from the Shanghai Science and Technology Commission (Grant 02DJ14006 ), the Key Project for New Drug Research from CAS, and the 863 Hi-Tech Program of China (Grants 2006AA020402 , 2006AA020602 ).
PY - 2009/10/15
Y1 - 2009/10/15
N2 - A series of benzamide derivatives which can simultaneously inhibit glycogen phosphorylase (GP) and activate glucokinase (GK) were prepared and evaluated. The structure-activity relationships (SAR) of these compounds were also presented. Among these, compounds 12, 13l, 13q, and 13v showed moderate activities towards both GK and GP. Compound 13h inhibited hLGP with an IC50 of 8.95 μM and activated GK with an EC50 of 1.87 μM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular docking simulation.
AB - A series of benzamide derivatives which can simultaneously inhibit glycogen phosphorylase (GP) and activate glucokinase (GK) were prepared and evaluated. The structure-activity relationships (SAR) of these compounds were also presented. Among these, compounds 12, 13l, 13q, and 13v showed moderate activities towards both GK and GP. Compound 13h inhibited hLGP with an IC50 of 8.95 μM and activated GK with an EC50 of 1.87 μM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular docking simulation.
KW - Dual action
KW - Glucokinase (GK) activators
KW - Glycogen phosphorylase (GP) inhibitors
KW - Type 2 diabetes
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U2 - 10.1016/j.bmc.2009.08.045
DO - 10.1016/j.bmc.2009.08.045
M3 - Article
C2 - 19758809
AN - SCOPUS:71749089240
SN - 0968-0896
VL - 17
SP - 7301
EP - 7312
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 20
ER -