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

Pharmacology & Toxicology

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

32 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 (US)
Pages (from-to)	2982-2991
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

Keywords

Aminothiazole
Benzamide derivatives
Glucokinase activator
Privileged-fragment-merging
Type 2 diabetes (T2D)

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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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.",

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AU - Mao, Weiwei

AU - Ning, Mengmeng

AU - Liu, Zhiqing

AU - Zhu, Qingzhang

AU - Leng, Ying

AU - Zhang, Ao

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KW - Privileged-fragment-merging

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