N 4-(3-bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d] pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation

Aleem Gangjee, Nilesh Zaware, Sudhir Raghavan, Jie Yang, Jessica E. Thorpe, Michael A. Ihnat

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

With the goal of developing multitargeted receptor tyrosine kinase inhibitors that display potent inhibition against PDGFRβ and VEGFR-2 we designed and synthesized eleven N 4-(3-bromophenyl)-7- (substitutedbenzyl) pyrrolo[2,3-d]pyrimidines 9a-19a. These compounds were obtained from the key intermediate N 4-(3-bromophenyl)-7H-pyrrolo[2,3- d]pyrimidine-2,4-diamine 29. Various arylmethyl groups were regiospecifically attached at the N7 of 29 via sodium hydride induced alkylation with substituted arylmethyl halides. Compounds 11a and 19a were potent dual inhibitors of PDGFRβ and VEGFR-2. In a COLO-205, in vivo tumor mouse model 11a demonstrated inhibition of tumor growth, metastasis, and tumor angiogenesis that was better than or comparable to the standard compound TSU-68 (SU6668, 8).

Original languageEnglish (US)
Pages (from-to)2444-2454
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number7
DOIs
StatePublished - Apr 1 2012

Keywords

  • Antiangiogenic agents
  • Multiple receptor
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'N <sup>4</sup>-(3-bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d] pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation'. Together they form a unique fingerprint.

Cite this