TY - JOUR
T1 - Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity
AU - Fuse, Shinichiro
AU - Suzuki, Kensuke
AU - Kuchimaru, Takahiro
AU - Kadonosono, Tetsuya
AU - Ueda, Hiroki
AU - Sato, Shinichi
AU - Kizaka-Kondoh, Shinae
AU - Nakamura, Hiroyuki
N1 - Funding Information:
We thank Mr. Yoshihisa Sei (Technical Department, Tokyo Institute of Technology) for his technical assistance with X-ray crystallographic analysis. This study was partially supported by Scientific Research (B) (No. 18H02685) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors declare no competing interests.
Funding Information:
We thank Mr. Yoshihisa Sei (Technical Department, Tokyo Institute of Technology) for his technical assistance with X-ray crystallographic analysis. This study was partially supported by Scientific Research (B) (No. 18H02685 ) from the Ministry of Education, Culture, Sports, Science and Technology, Japan .
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Cancer chemotherapy
KW - Fused-ring
KW - Hypoxia-inducible factor-1
KW - Indenopyrazolone
KW - Pyrazole
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U2 - 10.1016/j.bmc.2019.115207
DO - 10.1016/j.bmc.2019.115207
M3 - Article
C2 - 31740202
AN - SCOPUS:85075376468
VL - 28
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 1
M1 - 115207
ER -
