Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity

Shinichiro Fuse, Kensuke Suzuki, Takahiro Kuchimaru, Tetsuya Kadonosono, Hiroki Ueda, Shinichi Sato, Shinae Kizaka-Kondoh, Hiroyuki Nakamura

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

HIF-1 is regarded as a promising target for the drugs used in cancer chemotherapy, and creating readily accessible templates for the development of synthetic drug candidates that could inhibit HIF-1 transcriptional activity is an important pursuit. In this study, indeno[2,1-c]pyrazolones were designed as readily available synthetic inhibitors of HIF-1 transcriptional activity. Nine compounds were synthesized in 4–5 steps from commercially available starting materials. In evaluations of the ability to inhibit the hypoxia-induced transcriptional activity of HIF-1, compound 3c showed a higher level compared with that of known inhibitor, YC-1. The compound 3c suppressed HIF-1α protein accumulation without affecting the levels of HIF-1α mRNA.

Original languageEnglish
Article number115207
JournalBioorganic and Medicinal Chemistry
Volume28
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1
Externally publishedYes

Keywords

  • Cancer chemotherapy
  • Fused-ring
  • Hypoxia-inducible factor-1
  • Indenopyrazolone
  • Pyrazole

ASJC Scopus subject areas

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

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