107833-28-3

Upstream product

• 5503-73-1 2-amino-3-cyano-4,5-diphenylfuran 
• 2258-42-6 formyl acetic anhydride 
• 64-18-6 formic acid 
• 119-53-9 2-hydroxy-2-phenylacetophenone 

Downstream Products

• 873305-35-2 5,6-diphenyl-4-[(S)-(tetrahydrofuran-2-yl)-methyl]aminofuro[2,3-d]pyrimidine 
• 65148-07-4 4-chloro-5,6-diphenylfuro[2,3-d]pyrimidine 
• 106561-29-9 5,6-diphenyl-3H-furo[2,3-d]pyrimidin-4-one 

Relevant academic research and scientific papers

Structure-based design of novel Chk1 inhibitors: Insights into hydrogen bonding and protein-ligand affinity

We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP

CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and aurora A

The increased resistance of hypoxic cells to all forms of cancer therapy presents a major barrier to the successful treatment of most solid tumors. Inhibition of the essential kinase Checkpoint kinase 1 (Chk1) has been described as a promising cancer therapy for tumors with high levels of hypoxia-induced replication stress. However, as inhibition of Chk1 affects normal replication and induces DNA damage, these agents also have the potential to induce genomic instability and contribute to tumorigenesis. To overcome this problem, we have developed a bioreductive prodrug, which functions as a Chk1/Aurora A inhibitor specifically in hypoxic conditions. To achieve this activity, a key functionality on the Chk1 inhibitor (CH-01) is masked by a bioreductive group, rendering the compound inactive as a Chk1/Aurora A inhibitor. Reduction of the bioreductive group nitro moiety, under hypoxic conditions, reveals an electron-donating substituent that leads to fragmentation of the molecule, affording the active inhibitor. Most importantly, we show a significant loss of viability in cancer cell lines exposed to hypoxia in the presence of CH-01. This novel approach targets the most aggressive and therapy-resistant tumor fraction while protecting normal tissue from therapy-induced genomic instability.

METHODS FOR THE TREATMENT OF DISORDERS RELATED TO PHOSPHORYLATION OF HISTONES

Methods for disease diagnosis, prognosis and therapy selection. Compositions for use in these methods and selected therapies for treatment are also disclosed.