849814-02-4

Basic information

• Product Name: C₂₃H₂₈F₂N₄O₇
• Synonyms: C₂₃H₂₈F₂N₄O₇
• CAS NO: 849814-02-4
• Molecular Weight: 510.495
• Mol File: 849814-02-4.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: C₂₃H₂₈F₂N₄O₇(CAS DataBase Reference)
• NIST Chemistry Reference: C₂₃H₂₈F₂N₄O₇(849814-02-4)
• EPA Substance Registry System: C₂₃H₂₈F₂N₄O₇(849814-02-4)

Safety Data

• Hazardous Substances Data: 849814-02-4(Hazardous Substances Data)

Upstream product

• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 95058-81-4 gemcitabine 
• 1609205-97-1 4-allyloxycarbonylamino-1-[(2R,4R,5R)-4-allyloxycarbonyloxy-3,3-difluoro-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one 

Downstream Products

• 688008-85-7 5'-O-L-phenylalanylgemcitabine 

Relevant articles and documents

Potential development of Tumor-targeted oral Anti-cancer prodrugs: Amino acid and dipeptide monoester prodrugs of gemcitabine

One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine. The activation of all gemcitabine prodrugs was faster in pancreatic cell homogenates than their hydrolysis in buffer, suggesting enzymatic action. All prodrugs exhibited great stability in HFF cell homogenate, enhanced resistance to glycosidic bond metabolism by thymidine phosphorylase, and deamination by cytidine deaminase compared to their parent drug. All gemcitabine prodrugs exhibited higher uptake in HFF cells and better permeability across HFF monolayers than gemcitabine, suggesting a better delivery to tumor sites. Cell antiproliferative assays in Panc-1 and Capan-2 pancreatic ductal cell lines indicated that the gemcitabine prodrugs were more potent than their parent drug gemcitabine. The transport and enzymatic profiles of gemcitabine prodrugs suggest their potential for delayed enzymatic bioconversion and enhanced resistance to metabolic enzymes, as well as for enhanced drug delivery to tumor sites, and cytotoxic activity in cancer cells. These attributes would facilitate the prolonged systemic circulation and improved therapeutic efficacy of gemcitabine prodrugs.

The development of orally administrable gemcitabine prodrugs with d-enantiomer amino acids: Enhanced membrane permeability and enzymatic stability

Gemcitabine prodrugs with d- and l-configuration amino acids were synthesized and their chemical stability in buffers, resistance to glycosidic bond metabolism, enzymatic activation, permeability in Caco-2 cells and mouse intestinal membrane, anti-prolife