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

Bioorganic & medicinal chemistry 2020 Jan 01

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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. Copyright © 2019 Elsevier Ltd. All rights reserved.

Citation

Shinichiro Fuse, Kensuke Suzuki, Takahiro Kuchimaru, Tetsuya Kadonosono, Hiroki Ueda, Shinichi Sato, Shinae Kizaka-Kondoh, Hiroyuki Nakamura. Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity. Bioorganic & medicinal chemistry. 2020 Jan 01;28(1):115207