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

30 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 languageEnglish (US)
Pages (from-to)2982-2991
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number9
DOIs
StatePublished - 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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