Synthesis and in vitro biological evaluation of new pyrimidines as glucagon-like peptide-1 receptor agonists

Shaikha S. AlNeyadi, Abdu Adem, Naheed Amer, Alaa A. Salem, Ibrahim M. Abdou

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small-molecule GLP-1 receptor agonists. In this study, two series of new pyrimidine derivatives were designed and synthesized using an efficient route, and were evaluated in terms of GLP-1 receptor agonist activity. In the first series, novel pyrimidines substituted at positions 2 and 4 with groups varying in size and electronic properties were synthesized in a good yield (78–90%). In the second series, the designed pyrimidine templates included both urea and Schiff base linkers, and these compounds were successfully produced with yields of 77–84%. In vitro experiments with cultured cells showed that compounds 3a and 10a (10−15–10−9 M) significantly increased insulin secretion compared to that of the control cells in both the absence and presence of 2.8 mM glucose; compound 8b only demonstrated significance in the absence of glucose. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1 receptor agonists that can be administered orally.

Original languageEnglish
Pages (from-to)5071-5075
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number22
Publication statusPublished - Nov 15 2017


  • GLP-1
  • Insulin secretion
  • Pyrimidine analog
  • Type 2 diabetes

ASJC Scopus subject areas

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


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