(o- and p-Nitrobenzyloxycarbonyl)-5-fluorouracil derivatives as potential conjugated bioreductive alkylating agents.

doi:10.1021/JM00151A014

Paper

(o- and p-Nitrobenzyloxycarbonyl)-5-fluorouracil derivatives as potential conjugated bioreductive alkylating agents.

Published 1986 · T S Lin, L Wang, I Antonini

Journal of medicinal chemistry

Q1 SJR score

16

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

A series of (o- and p-nitrobenzyloxycarbonyl)-5-fluorouracil derivatives were synthesized by reacting o- or p-nitrobenzyl chloroformate with 5-fluorouracil in the presence of triethylamine in DMF or Me2SO. The reductive activation of these agents was hypothesized to generate a reactive methide and 5-fluorouracil, two components that are capable of synergistic interaction through complementary inhibition. Measurement of the surviving fractions of EMT6 tumor cells treated with these agents in culture under conditions of hypoxia and aerobiosis resulted in equal cell kill regardless of the state of oxygenation. One of the synthesized agents, 3-(p-nitrobenzyloxycarbonyl)-5-fluorouracil (4), appeared to be superior to 5-fluorouracil in prolonging the survival time of mice bearing intraperitoneal implants of the P388 leukemia and Sarcoma 180.

Study Snapshot

Synthesized (o- and p-nitrobenzyloxycarbonyl)-5-fluorouracil derivatives show potential as effective bioreductive alkylating agents for treating various cancers, with 3-(p-nitrobenzyloxycarbonyl)-5-fluorouracil (4) showing

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

(o- and p-Nitrobenzyloxycarbonyl)-5-fluorouracil derivatives as potential conjugated bioreductive alkylating agents.

Sign up to use Study Snapshot

References

Citations

Synthesis, crystal structure, Hirshfeld surface and interaction energies analysis of 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione

The crystal packing of 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione is stabilized by intermolecular hydrogen bond, and CH stacking interactions, with OH (37.1%), HH (2

Conjugatable and Bioreduction Cleavable Linker for the 5'-Functionalization of Oligonucleotides.

The developed conjugatable and bioreduction cleavable linker effectively enables the 5'-functionalization of oligonucleotides, enabling diverse functionalization reactions.

Synthesis and evaluation of (18)F-labeled 4-nitrobenzyl derivatives for imaging tumor hypoxia with positron emission tomography: Comparison of 2-[(18)F]fluoroethyl carbonate and 2-[(18)F]fluoroethyl carbamate.

2-[(18)F]fluoroethyl carbonate and 2-[(18)F]fluoroethyl carbamate show good tumor uptake but are not suitable for imaging tumor hypoxia due to suboptimal tumor-to-background contrasts.

Bioreductive deprotection of 4-nitrobenzyl group on thymine base in oligonucleotides for the activation of duplex formation.

Deprotection of thymine residues in modified oligonucleotides under bioreductive conditions allows them to form stable duplexes with target oligonucleotides, potentially acting as prodrugs against hypoxic cells.

Synthesis, In Vitro Cytotoxicity and Radiosensitizing Activity of Novel 3‐[(2,4‐Dinitrophenylamino)Alkyl] Derivatives of 5‐Fluorouracil

Novel 3[(2,4-dinitrophenylamino)-alkyl] derivatives of 5fluorouracil show selective and concentration-dependent radiocytotoxicity under hypoxic conditions, while having no significant effect under aerobic conditions.