- Bisphosphonate conjugates and methods of making and using the same
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The present invention is directed to particular bisphosphonate compounds, and in particular, to bisphosphonate conjugates that are useful in the treatment of soft tissues surrounding bone and bone-related diseases, such as bone cancer and osteoporosis.
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Page column 10
(2008/06/13)
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- Potentiation of the antitumor effect of 5-fluoro-2'-deoxyuridine esters in combination with acyclothymidine esters on L1210 in mice via oral administration
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Fifteen pyrimidine-related compounds were evaluated for their ability to inhibit enzymatic degradation of 5-fluoro-2'-deoxyuridine (FUdR). Acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed the highest inhibitory effect on the phosphorolytic degradation of FUdR in various tissue homogenates derived from mouse, rat, and beagle organs. Both the drug (FUdR) and the inhibitor (acyclothymidine) were esterified with appropriate aliphatic acids in order to synchronize their behavior after simultaneous oral administration. The antitumor activity of orally administered FUdR esters was potentiated by the simultaneous oral administration of the acyclothymidine esters, but not by acyclothymidine.
- Kawaguchi,Saito,Saneyoshi
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p. 939 - 943
(2007/10/02)
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- Novel uracil derivatives, process for preparing the same and a pharmaceutical composition containing the same
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Novel uracil derivatives of the formula STR1 (wherein R1, R2 R3 and X are defined in the description) and their pharmaceutically acceptable salts, process for preparing the same and pharmaceutical composition containing the same are disclosed. The uracil derivatives have good antitumor activity and, therefore, are useful as antitumor preparation.
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- Synthesis and Biological Effects of Acyclic Pyrimidine Nucleoside Analogues
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A series of nucleoside analogues has been prepared, wherein the cyclic carbohydrate moiety is replaced by aliphatic side chains attached to cytosine, thymine, uracil, and 5-fluorouracil.The 1- derivatives of these heterocycles were synthesized by reacting the silylated bases with 2-(chloromethoxy)ethyl benzoate, followed by removal of the protecting groups with methanolic ammonia.The hydroxy group of a number of these derivatives was subsequently replaced by an azido, amino, or carbamoyloxy moiety.The 1-(2-oxo-3-butyl) and 1-(2-oxo-3-nonyl)derivatives of cytosine were also prepared, their synthesis being accomplished by condensation of the silylated heterocycle with the appropriate α-halo ketone.At 10-4 M concentrations, the newly prepared compounds were inactive against leukemia L-1210 cells in culture.However, a number of the agents inhibited the in vitro growth of Escherichia coli K-12, the most potent among these, 1--5-fluorouracil, being active at an IC50 of 1.2 μM.This compound was equally active in preventing the growth of a 5-fluorouracil resistant strain of E. coli.Some of the analogues were also found the selectively interfere with herpes simplex virus replication in vitro.None of the cytosine derivatives tested served as either substrates or inhibitors of human liver citosine nucleoside deaminase.
- Schroeder, Alan C.,Hughes, Robert G.,Bloch, Alexander
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p. 1078 - 1083
(2007/10/02)
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- Pyrimidine Acyclic Nucleosides. 1-pyrimidines as Candidate Antivirals
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A number of pyrimidine acyclic nucleosides were synthesized and tested for activity against herpes simplex virus type 1.Synthesis of 1-cytosine (8) and 1-uracil (14) was accomplished in two or three steps
- Kelley, James L.,Kelsey, John E.,Hall, William R.,Krochmal, Mark P.,Schaeffer, Howard J.
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p. 753 - 756
(2007/10/02)
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- ANALOGS OF PYRIMIDINE NUCLEOSIDES. 14. SYNTHESIS AND ANTITUMORIGENIC ACTIVITY OF ALKOXYALKYL DERIVATIVES OF 5-FLUOROURACIL
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A number of alkoxyalkyl derivatives of 5-fluorouracil were synthesized by alkylation of 2,4-bis(trimethylsilyl)-5-fluorouracil with α-chloro ethers or by the addition of 5-fluorouracil to vinyl ethers.It was established that the synthesized compounds are capable of increasing the lifetimes of mice with L-1210 leukemia and La hemocytoblastosis.The UV and NMR spectra of the synthesized compounds are presented.
- Karpeiskii, M. Ya.,Mikhailov, S. M.,Tsieminya, A. S.,Ziderman, A. A.,Kravchenko, I. M.,et al.
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p. 1176 - 1179
(2007/10/02)
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