309742-24-3

Basic information

• Product Name: 2-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)sulfanyl]-N-phenylacetamide
• Synonyms: 2-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)sulfanyl]-N-phenylacetamide
• CAS NO: 309742-24-3
• Molecular Formula: C15H17N3O2S
• Molecular Weight: 303.37938
• Mol File: 309742-24-3.mol

Chemical Properties

• Appearance: /
• Density: 1.26±0.1 g/cm3(Predicted)
• PKA: 8.16±0.50(Predicted)
• CAS DataBase Reference: 2-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)sulfanyl]-N-phenylacetamide(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)sulfanyl]-N-phenylacetamide(309742-24-3)
• EPA Substance Registry System: 2-[(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)sulfanyl]-N-phenylacetamide(309742-24-3)

Safety Data

• Hazardous Substances Data: 309742-24-3(Hazardous Substances Data)

Upstream product

• 51-52-5 propylthiouracil 
• 5326-87-4 N-(phenyl)bromoacetamide 
• 62-53-3 aniline 

Relevant articles and documents

MATRIX METALLOPROTEINASE-9 HEMOPEXIN DOMAIN INHIBITORS AND METHODS OF TREATMENT USING SAME

Small molecule inhibitors are claimed that selectively target the hemopexin domain of matrix metalloproteinase 9 (MMP-9) and do not inhibit the protease's catalytic functions. A method of treating cancer in a patient in need thereof with the compounds of the invention is also claimed.

Targeting the Hemopexin-like Domain of Latent Matrix Metalloproteinase-9 (proMMP-9) with a Small Molecule Inhibitor Prevents the Formation of Focal Adhesion Junctions

A lack of target specificity has greatly hindered the success of inhibitor development against matrix metalloproteinases (MMPs) for the treatment of various cancers. The MMP catalytic domains are highly conserved, whereas the hemopexin-like domains of MMPs are unique to each family member. The hemopexin-like domain of MMP-9 enhances cancer cell migration through self-interaction and heterointeractions with cell surface proteins including CD44 and α4β1 integrin. These interactions activate EGFR-MAP kinase dependent signaling that leads to cell migration. In this work, we generated a library of compounds, based on hit molecule N-[4-(difluoromethoxy)phenyl]-2-[(4-oxo-6-propyl-1H-pyrimidin-2-yl)sulfanyl]-acetamide, that target the hemopexin-like domain of MMP-9. We identify N-(4-fluorophenyl)-4-(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-ylthio)butanamide, 3c, as a potent lead (Kd = 320 nM) that is specific for binding to the proMMP-9 hemopexin-like domain. We demonstrate that 3c disruption of MMP-9 homodimerization prevents association of proMMP-9 with both α4β1 integrin and CD44 and results in the dissociation of EGFR. This disruption results in decreased phosphorylation of Src and its downstream target proteins focal adhesion kinase (FAK) and paxillin (PAX), which are implicated in promoting tumor cell growth, migration, and invasion. Using a chicken chorioallantoic membrane in vivo assay, we demonstrate that 500 nM 3c blocks cancer cell invasion of the basement membrane and reduces angiogenesis. In conclusion, we present a mechanism of action for 3c whereby targeting the hemopexin domain results in decreased cancer cell migration through simultaneous disruption of α4β1 integrin and EGFR signaling pathways, thereby preventing signaling bypass. Targeting through the hemopexin-like domain is a powerful approach to antimetastatic drug development.