Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators

Weiwei Mao; Mengmeng Ning; Zhiqing Liu; Qingzhang Zhu; Ying Leng; Ao Zhang

doi:10.1016/j.bmc.2012.03.008

Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators

Weiwei Mao, Mengmeng Ning, Zhiqing Liu, Qingzhang Zhu, Ying Leng, Ao Zhang

Internal Medicine

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

49 Scopus citations

Abstract

A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.

Original language	English
Pages (from-to)	2982-91
Number of pages	10
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	9
DOIs	https://doi.org/10.1016/j.bmc.2012.03.008
State	Published - May 1 2012

Bibliographical note

Keywords

Animals
Benzamides/blood
Biological Availability
Drug Design
Enzyme Activation/drug effects
Glucokinase/chemistry
Hypoglycemic Agents/blood
Mice
Mice, Inbred ICR
Structure-Activity Relationship
Thiazoles/blood

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title = "Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators",

abstract = "A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.",

keywords = "Animals, Benzamides/blood, Biological Availability, Drug Design, Enzyme Activation/drug effects, Glucokinase/chemistry, Hypoglycemic Agents/blood, Mice, Mice, Inbred ICR, Structure-Activity Relationship, Thiazoles/blood",

author = "Weiwei Mao and Mengmeng Ning and Zhiqing Liu and Qingzhang Zhu and Ying Leng and Ao Zhang",

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T1 - Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators

AU - Mao, Weiwei

AU - Ning, Mengmeng

AU - Liu, Zhiqing

AU - Zhu, Qingzhang

AU - Leng, Ying

AU - Zhang, Ao

PY - 2012/5/1

Y1 - 2012/5/1

N2 - A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.

AB - A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.

KW - Animals

KW - Benzamides/blood

KW - Biological Availability

KW - Drug Design

KW - Enzyme Activation/drug effects

KW - Glucokinase/chemistry

KW - Hypoglycemic Agents/blood

KW - Mice

KW - Mice, Inbred ICR

KW - Structure-Activity Relationship

KW - Thiazoles/blood

U2 - 10.1016/j.bmc.2012.03.008

DO - 10.1016/j.bmc.2012.03.008

M3 - Article

C2 - 22459213

SN - 0968-0896

VL - 20

SP - 2982

EP - 2991

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 9

ER -

Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators

Abstract

Bibliographical note

Keywords

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