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

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

  • Bioorg Med Chem. 2020 Jan 1;28(1):115207. doi: 10.1016/j.bmc.2019.115207.
Shinichiro Fuse 1,  Kensuke Suzuki 2,  Takahiro Kuchimaru 3,  Tetsuya Kadonosono 3,  Hiroki Ueda 2,  Shinichi Sato 1,  Shinae Kizaka-Kondoh 3,  Hiroyuki Nakamura 4
Affiliations

Affiliations

  • 1 Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
  • 2 Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan; School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
  • 3 School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
  • 4 Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan. Electronic address: [email protected].
PMID: 31740202 DOI: 10.1016/j.bmc.2019.115207
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.

Keywords

Cancer chemotherapy; Fused-ring; Hypoxia-inducible factor-1; Indenopyrazolone; Pyrazole.

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