Simple Transformation of Thymine 1-[3-Hydroxy-2-(phosphonomethoxy)propyl] Derivatives to Their 1-[3-Fluoro-2-(phosphonomethoxy)propyl] Counterparts

2005 ◽  
Vol 70 (9) ◽  
pp. 1465-1481 ◽  
Author(s):  
Karel Pomeisl ◽  
Radek Pohl ◽  
Antonín Holý ◽  
Ivan Votruba
Keyword(s):  
Hydroxy Group ◽  
Thymidine Phosphorylase ◽  
Simple Transformation ◽  
Acyclic Nucleoside Phosphonates ◽  
Novel Method ◽  
Acyclic Nucleoside ◽  
Sulfonyl Fluoride

A novel method of transformation of HOCH2 group to FCH2 was successfully applied to the preparation of fluorine-containing pyrimidine acyclic nucleoside phosphonates (FPMP compounds) such as (S)- and (R)-1-[3-fluoro-2-(phosphonomethoxy)propyl]thymine (7a, 7b) (FPMPT). The key displacement of hydroxy group with fluorine in 1-{2-[(diisopropoxyphosphoryl)- methoxy]-3-hydroxypropyl}-4-methoxy-5-methylpyrimidin-2(1H)-one (5a, 5b) was performed using perfluorobutane-1-sulfonyl fluoride in the presence of DBU. Novel pyrimidine acyclic nucleoside phosphonates were investigated as inhibitors of thymidine phosphorylase.

Syntheses of Base and Side-Chain Modified Pyrimidine 1-[2-(Phosphonomethoxy)propyl] Derivatives as Potent Inhibitors of Thymidine Phosphorylase (PD-ECGF) from SD-Lymphoma

2006 ◽  
Vol 71 (4) ◽  
pp. 595-624 ◽  
Author(s):  
Karel Pomeisl ◽  
Ivan Votruba ◽  
Antonín Holý ◽  
Radek Pohl
Keyword(s):  
Thymidine Phosphorylase ◽  
Cell Lymphoma ◽  
Inhibitory Effect ◽  
Side Chain ◽  
The Novel ◽  
Inhibitory Potency ◽  
Methyl Group ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Trifluoromethyl Groups

In this study we synthesized a series of thymine and 5-ethyluracil acyclic nucleoside phosphonates bearing hydroxymethyl, methoxymethyl, azidomethyl, aminomethyl and (trimethylammonio)methyl group in side chain as potent inhibitors of thymidine phosphorylase. In addition, we investigated in particular the novel syntheses of fluorinated derivatives containing fluoromethyl or trifluoromethyl groups in side chain such as 5-ethyl- 1-[(S)-3-fluoro-2-(phosphonomethoxy)propyl]uracil (8) or 5-ethyl-1-[3,3,3-trifluoro-2-(phosphonomethoxy)propyl]uracil and thymine derivatives 27 and 28. Uracil acyclic nucleoside phosphonates 1-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}uracil (12) and 1-{2-[(diisopropoxyphosphoryl)methoxy]-3,3,3-trifluoropropyl}uracil (19) were fluorinated to corresponding 5-fluorouracil derivatives. While the 5-fluorouracil derivatives exhibit a marginal inhibitory effect, thymine and 5-ethyluracil compound with fluorine in side chains possess considerable inhibitory potency toward thymidine phosphorylase from rat spontaneous T-cell lymphoma.

Efficient one-pot synthesis of polysubstituted 6-[(1H-1,2,3-triazol-1-yl)methyl]uracils through the “click” protocol

2011 ◽  
Vol 76 (9) ◽  
pp. 1121-1131 ◽  
Author(s):  
Petr Jansa ◽  
Petr Špaček ◽  
Ivan Votruba ◽  
Petra Břehová ◽  
Martin Dračínský ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Inhibitory Activity ◽  
Thymidine Phosphorylase ◽  
Room Temperature ◽  
One Pot ◽  
Decarboxylation Reaction ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Potential Inhibitors ◽  
Substituted 1

The preparation of several triazolo acyclic nucleosides and triazolo acyclic nucleoside phosphonates is described. The synthetic methodology has been developed as an efficient one-pot Cu(I)-catalyzed azide alkyne Huisgen “click” cycloaddition. A novel Cu(I)-catalyzed decarboxylation reaction of 1-substituted 1H-1,2,3-triazole-4-carboxylic acids at room temperature was observed and used for the preparation of 1-substituted 1H-1,2,3-triazoles. As congeners of TPI (Taiho pharmaceutical inhibitor), the prepared compounds were screened as potential inhibitors of human thymidine phosphorylase, but no inhibitory activity was observed.

Acyclic nucleoside phosphonates and human telomerase inhibition

2005 ◽  
Author(s):  
Miroslav Hájek ◽  
Naděžda Matulová ◽  
Ivan Votruba ◽  
Antonín Holý ◽  
Eva Tloušťová
Keyword(s):  
Telomerase Inhibition ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Human Telomerase

Tyrosine-based prodrugs of acyclic nucleoside phosphonates

2014 ◽  
Author(s):  
Tomáš Tichý ◽  
Karel Pomeisl ◽  
Marcela Krečmerová ◽  
Charles E. McKenna
Keyword(s):  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside
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