Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase

Lei Zhang; Honglin Li; Qingzhang Zhu; Jun Liu; Ling Chen; Ying Leng; Hualiang Jiang; Hong Liu

doi:10.1016/j.bmc.2009.08.045

Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase

Lei Zhang, Honglin Li, Qingzhang Zhu, Jun Liu, Ling Chen, Ying Leng, Hualiang Jiang, Hong Liu

Internal Medicine

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

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 IC(50) of 8.95 microM and activated GK with an EC(50) of 1.87 microM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular docking simulation.

Original language	English
Pages (from-to)	7301-12
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	20
DOIs	https://doi.org/10.1016/j.bmc.2009.08.045
State	Published - Oct 15 2009

Keywords

Benzamides/chemistry
Enzyme Activation
Glucokinase/metabolism
Glycogen Phosphorylase/antagonists & inhibitors
Humans
Hypoglycemic Agents/chemistry
Structure-Activity Relationship

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10.1016/j.bmc.2009.08.045

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title = "Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase",

abstract = "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 IC(50) of 8.95 microM and activated GK with an EC(50) of 1.87 microM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular docking simulation.",

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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

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 IC(50) of 8.95 microM and activated GK with an EC(50) of 1.87 microM. 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 IC(50) of 8.95 microM and activated GK with an EC(50) of 1.87 microM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular docking simulation.

KW - Benzamides/chemistry

KW - Enzyme Activation

KW - Glucokinase/metabolism

KW - Glycogen Phosphorylase/antagonists & inhibitors

KW - Humans

KW - Hypoglycemic Agents/chemistry

KW - Structure-Activity Relationship

U2 - 10.1016/j.bmc.2009.08.045

DO - 10.1016/j.bmc.2009.08.045

M3 - Article

C2 - 19758809

SN - 0968-0896

VL - 17

SP - 7301

EP - 7312

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 20

ER -

Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase

Abstract

Keywords

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