Chrome Extension
WeChat Mini Program
Use on ChatGLM

Pyrazolo[4,3-d]pyrimidine Derivatives as a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Domain Inhibitor for the Treatment of Anemia

Takashi Goi,Tatsuo Nakajima, Yoshiyuki Komatsu, Atsushi Kawata,Shuhei Yamakoshi,Okimasa Okada, Masakatsu Sugahara, Asami Umeda, Yoko Takada,Jun Murakami,Rikiya Ohashi,Tomoko Watanabe,Koichi Fukase

ACS medicinal chemistry letters(2020)

Cited 8|Views7
No score
Abstract
Inhibition of hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) promotes erythropoietin (EPO) production by stabilizing the HIF alpha subunit. Thieno[2,3-d]-pyrimidine 8 identified based on X-ray crystal structure analysis was optimized to lead to the discovery of pyrazolo[4,3-d]-pyrimidine 13 as the lead compound of orally bioavailable HIF-PHD inhibitors. Conversion of the benzyl moiety in 13 gave pyrazolopyrimidine 19 with high solubility and bioavailability, which increased hemoglobin levels in anemic model rats after repeated oral administration. It was shown that pyrazolo[4,3-d]pyrimidine derivatives are promising therapeutic agents for renal anemia through the inhibition of HIF-PHD.
More
Translated text
Key words
renal anemia,hypoxia-inducible factor prolyl hydroxylase domain inhibitor,erythropoietin,pyrazolopyrimidine,solubility
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined