Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-09-15
1997-12-09
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
435 89, 536 268, 536 2852, A61K 3170, C07H 19207
Patent
active
056960972
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel 2'-methylidene-nucleotide compounds and salts thereof having superior antitumor effect and useful as pharmaceuticals, methods for production thereof, pharmaceutical compositions comprising same as an effective ingredient and methods for treating tumor.
2. Description of Related Art
Nucleoside antitumor agents have been conventionally used for an extensive range of clinical situations against various tumors, but are associated with the following problems. That is, while the activity of said antitumor agents is expressed upon phosphorylation of 5'-position hydroxy, the agents are susceptible to decomposition into inactive substances by phosphorolysis, deamination and so on; the tumor cells come to have resistance to said antitumor agents; and the agents show toxicity to normal cells as well.
Hence, nucleoside antitumor agents free of these problems are desired.
An object of the present invention is to solve the above-mentioned problems and to provide novel 2'-methylidenenucleotide compounds superior to known nucleoside antitumor agents in properties, methods for production thereof and pharmaceutical use thereof.
SUMMARY OF THE INVENTION
The present inventors have conducted intensive studies in an effort to accomplish the aforementioned object, and found that novel 2'-methylidenenucleotide compounds of the formula (I) to be shown below and salts thereof have extremely superior properties.
The present invention has been completed based on the above finding, and relates to 2'-methylidenenucleotide compounds of the formula (I) ##STR2## wherein residue or a hydrocarbon residue; and halogen or an alkyl,
Of the compounds of the formula (I), the present invention particularly relates to 2'-methylidenenucleotide compounds wherein R, R.sup.3 and R.sup.4 are each hydrogen, 2'-methylidene-nucleotide compounds wherein R is fluorine, and R.sup.3 and R.sup.4 are each hydrogen, 2'-methylidenenucleotide compounds wherein R, R.sup.3 and R.sup.4 are each hydrogen, and R.sup.1 and R.sup.2 are the same fatty acid residues, 2'-methylidenenucleotide compounds wherein R is fluorine, R.sup.3 and R.sup.4 are each hydrogen, and R.sup.1 and R.sup.2 are the same fatty acid residues, 2'-methylidenenucleotide compounds wherein R, R.sup.3 and R.sup.4 are each hydrogen, and R.sup.1 and R.sup.2 are the same fatty acid residues having 12 to 20 carbon atoms, 2'-methylidenenucleotide compounds wherein R is fluorine, R.sup.3 and R.sup.4 are each hydrogen, and R.sup.1 and R.sup.2 are the same fatty acid residues having 12 to 20 carbon atoms, and salts thereof.
The present invention also relates to methods for producing 2'-methylidenenucleotide compounds of the above-mentioned formula (I) and salts thereof, comprising reacting a phospholipid of the formula (II) ##STR3## wherein R.sup.1 and R.sup.2 are as defined above, and R.sup.5 is a choline residue, with a nucleoside of the formula (III) ##STR4## wherein R, R.sup.3 and R.sup.4 are as defined above, in the presence of a phospholipase D.
The present invention also relates to pharmaceutical compositions comprising a 2'-methylidenenucleotide compound of the aforementioned formula (I) or a salt thereof, and a pharmaceutically acceptable carrier. The present invention also relates to methods for treating tumor, comprising administering an effective amount of a 2'-methylidenenucleotide compound of the aforementioned formula (I) or a salt thereof to mammals inclusive of human in need of treating tumor.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENT
In the present specification, halogen represented by R, R.sup.3 and R.sup.4 means fluorine, chlorine, bromine and iodine.
The fatty acid residue represented by R.sup.1 and R.sup.2 means that having 2 to 30, preferably 10-24 and more preferably 12-20 carbon atoms, and may be a saturated fatty acid residue or an unsaturated fatty acid residue. Specific examples of the fatty acid residue include saturated fatty acid residues such as lauroyl, myristoyl, palmitoyl, s
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Fujii Akihiro
Matsuda Akira
Miyashita Takanori
Ono Takashi
Sakata Shinji
Crane L. Eric
Kight John
Matsuda Akira
Sasaki Takuma
Yamasa Corporation
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