1257335-47-9

Basic information

• Product Name: (E)-3-(1-(3-(4-bromophenyl)propyl)-2-oxo-1,2-dihydropyridin-3-yl)-N-hydroxyacrylamide
• Synonyms: (E)-3-(1-(3-(4-bromophenyl)propyl)-2-oxo-1,2-dihydropyridin-3-yl)-N-hydroxyacrylamide
• CAS NO: 1257335-47-9
• Molecular Weight: 377.238
• Mol File: 1257335-47-9.mol

Chemical Properties

• CAS DataBase Reference: (E)-3-(1-(3-(4-bromophenyl)propyl)-2-oxo-1,2-dihydropyridin-3-yl)-N-hydroxyacrylamide(CAS DataBase Reference)
• NIST Chemistry Reference: (E)-3-(1-(3-(4-bromophenyl)propyl)-2-oxo-1,2-dihydropyridin-3-yl)-N-hydroxyacrylamide(1257335-47-9)
• EPA Substance Registry System: (E)-3-(1-(3-(4-bromophenyl)propyl)-2-oxo-1,2-dihydropyridin-3-yl)-N-hydroxyacrylamide(1257335-47-9)

Safety Data

• Hazardous Substances Data: 1257335-47-9(Hazardous Substances Data)

Upstream product

• 90562-10-0 trans-1-(3-bromopropyl)-4-bromobenzene 
• 36404-89-4 2-oxo-1,2-dihydro-pyridine-3-carbaldehyde 

Relevant articles and documents

Improving potency and metabolic stability by introducing an alkenyl linker to pyridine-based histone deacetylase inhibitors for orally available RUNX3 modulators

RUNX3, a tumor suppressor, is suppressed in various cancers by abnormal epigenetic changes. Histone deacetylases (HDACs) can deacetylate the lysine residues of RUNX3, followed by degradation via a ubiquitin-mediated pathway. Inhibition of HDAC leads to functional restoration of the RUNX3 protein by epigenetic expression and RUNX3 protein stabilization. We previously reported a series of HDAC inhibitors that restored RUNX3 function. In the present study, we introduced an alkenyl linker group to pyridine-based HDAC inhibitors to improve their potencies and chemical properties. This alkenyl linker made the compounds more rigid, facilitating a better fit than alkyl moieties to the active site of HDAC proteins. Most compounds in this series exhibited potent RUNX activities, HDAC inhibitory activities, and inhibitory activities towards the growth of human cancer cell lines. Notably, one of these derivatives, (E)-3-(1-cinnamyl-2-oxo-1,2-dihydropyridin-3-yl)-N-hydroxyacrylamide (7k), showed excellent properties in a microsomal stability study, in a xenograft study, and in an in vivo pharmacokinetic evaluation. Modulation of RUNX3 therefore results in highly potent and orally available anticancer chemotherapeutic agents.

Discovery of orally available runt-related transcription factor 3 (RUNX3) modulators for anticancer chemotherapy by epigenetic activation and protein stabilization

Recently, we identified a novel strategy for anticancer chemotherapy by restoring runt-related transcription factor 3 (RUNX3) levels via lactam-based histone deacetylase (HDAC) inhibitors that stabilize RUNX3. Described here are the synthesis, biological evaluation, and pharmacokinetic evaluation of new synthetic small molecules based on pyridone-based HDAC inhibitors that specifically stabilize RUNX3 by acetylation and regulate its function. Many of the newly synthesized compounds showed favorable RUNX activities, HDAC inhibitory activities, and inhibitory activities on the growth of human cancer cell lines. Notably, one of these new derivatives, (E)-N-hydroxy-3-(2-oxo-1-(quinolin-2-ylmethyl)-1,2-dihydropyridin-3-yl)acrylamide (4l), significantly restored RUNX3 in a dose-dependent manner and showed high metabolic stability, a good pharmacokinetic profile with high oral bioavailability and long half-life, and strong antitumor activity. This study suggests that pyridone-based analogues modulate RUNX3 activity through epigenetic regulation as well as strong transcriptional and post-translational regulation of RUNX3 and could be potential clinical candidates as orally available RUNX3 modulators for the treatment of cancer.