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

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Title:Syntheses of Base and Side-Chain Modified Pyrimidine 1-[2-(Phosphonomethoxy)propyl] Derivatives as Potent Inhibitors of Thymidine Phosphorylase (PD-ECGF) from SD-Lymphoma
Creators:
Pomeisl, Karel
Votruba, Ivan
Holý, Antonín
Pohl, Radek
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 71, 4, pp. 595-624
Uncontrolled Keywords:Acyclic nucleoside phosphonates, Pyrimidines, Fluorination, Uracil, Thymidine phosphorylase, Nucleotides, Acyclic nucleotide analogues, Thymine

Abstract

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-[(<i>S</i>)-3-fluoro-2-(phosphonomethoxy)propyl]uracil (<strong>8</strong>) or 5-ethyl-1-[3,3,3-trifluoro-2-(phosphonomethoxy)propyl]uracil and thymine derivatives <strong>27</strong> and <strong>28</strong>. Uracil acyclic nucleoside phosphonates 1-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}uracil (<strong>12</strong>) and 1-{2-[(diisopropoxyphosphoryl)methoxy]-3,3,3-trifluoropropyl}uracil (<strong>19</strong>) 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. <p>

Title:Syntheses of Base and Side-Chain Modified Pyrimidine 1-[2-(Phosphonomethoxy)propyl] Derivatives as Potent Inhibitors of Thymidine Phosphorylase (PD-ECGF) from SD-Lymphoma
Creators:
Pomeisl, Karel
Votruba, Ivan
Holý, Antonín
Pohl, Radek
Uncontrolled Keywords:Acyclic nucleoside phosphonates, Pyrimidines, Fluorination, Uracil, Thymidine phosphorylase, Nucleotides, Acyclic nucleotide analogues, Thymine
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:71
Number:4
Page Range:pp. 595-624
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20060595UNSPECIFIED
ID Code:2494
Item Type:Article
Deposited On:06 Feb 2009 17:19
Last Modified:06 Feb 2009 16:19

Citation

Pomeisl, Karel; Votruba, Ivan; Holý, Antonín; Pohl, Radek (2006) Syntheses of Base and Side-Chain Modified Pyrimidine 1-[2-(Phosphonomethoxy)propyl] Derivatives as Potent Inhibitors of Thymidine Phosphorylase (PD-ECGF) from SD-Lymphoma. Collection of Czechoslovak Chemical Communications, 71 (4). pp. 595-624. ISSN 0010-0765

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