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

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2982-2991
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number9
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Glucokinase
Pharmacokinetics
Chemical activation
Pharmacology
Derivatives
Glucose
Merging
Plasmas
benzamide

Keywords

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

ASJC Scopus subject areas

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

Cite this

Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. / Mao, Weiwei; Ning, Mengmeng; Liu, Zhiqing; Zhu, Qingzhang; Leng, Ying; Zhang, Ao.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 9, 01.05.2012, p. 2982-2991.

Research output: Contribution to journalArticle

Mao, Weiwei ; Ning, Mengmeng ; Liu, Zhiqing ; Zhu, Qingzhang ; Leng, Ying ; Zhang, Ao. / Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 9. pp. 2982-2991.
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