Design, synthesis and preclinical evaluation of 5-methyl-N4-aryl-furo[2,3-d]pyrimidines as single agents with combination chemotherapy potential

Ravi Kumar Vyas Devambatla, Shruti Choudhary, Michael Ihnat, Ernest Hamel, Susan L. Mooberry, Aleem Gangjee

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The design, synthesis and biological evaluation of 4-substituted 5-methyl-furo[2,3-d]pyrimidines is described. The Ullmann coupling of 5-methyl-furo[2,3-d]pyrimidine with aryl iodides was successfully optimized to synthesize these analogs. Compounds 6–10 showed single-digit nanomolar inhibition of EGFR kinase. Compounds 1 and 6–10 inhibited VEGFR-2 kinase better than or equal to sunitinib. Compounds 1 and 3–10 were more potent inhibitors of PDGFR-β kinase than sunitinib. In addition, compounds 4–11 had higher potency in the CAM angiogenesis assay than sunitinib. Compound 1 showed in vivo efficacy in an A498 renal xenograft model in mice. Multiple RTK and tubulin inhibitory attributes of 1, 4, 6 and 8 indicates that these compounds may be valuable preclinical single agents targeting multiple intracellular targets.

Original languageEnglish (US)
Pages (from-to)3085-3093
Number of pages9
JournalBioorganic and Medicinal Chemistry Letters
Issue number18
StatePublished - Oct 1 2018


  • Angiogenesis
  • Combination chemotherapy
  • Furo[2,3-d]pyrimidines
  • Structure-activity relationships
  • Tubulin inhibitors

ASJC Scopus subject areas

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


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