CA1162853A - Medicaments containing 5-alkyl-pyrimidine nucleosides and use as cytostatic and virostatic agents - Google Patents
Medicaments containing 5-alkyl-pyrimidine nucleosides and use as cytostatic and virostatic agentsInfo
- Publication number
- CA1162853A CA1162853A CA000373253A CA373253A CA1162853A CA 1162853 A CA1162853 A CA 1162853A CA 000373253 A CA000373253 A CA 000373253A CA 373253 A CA373253 A CA 373253A CA 1162853 A CA1162853 A CA 1162853A
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- fluorouracil
- cytostatic
- formula
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
5-Alkyl-pyrimidine nucleosides of the formula:
5-Alkyl-pyrimidine nucleosides of the formula:
Description
' ^' 1 ' '':''" " ' :-; ll~S3 This invention relates to certain pharmacologically active 5-alkyl-pyrimidine nucleosides and to medicaments containing them, alone or in combination with 5-fluorouracil, as well as the use of said medicaments for treatment of malignant diseases, in immunosuppressive therapy, and as cytostatic and virostatic agents.
5-Fluorouracil is known as a cytostatically active substance. According to present knowledge, it is converted in the organism to fluorouracil riboside monophosphate and in major part built into the RNA. Only a small fraction of the fluorouracil riboside monophosphate is transformed into 5-fluorouracil deoxy-riboside monophosphate by the action of the enzyme pyridine nucleotide reductase and then phosphorylated into the corresonding triphosphate. For cytostatic action, it is known that fluorouracil deoxyriboside triphosphate is responsible. Namely, it is a strong inhibitor of thymidilate kinase and thus inhibits DNA synthesis.
This process is schematically shown below.
- -;; ~16~
~ ~ dT~lP-~ dTDP ~__dTTP --~DNS
O ~ N ~ ~
(FU = Fluorouracil) O O O ~ N
Nucleoside H2O3P-O-P-O-PI-O-cH2 phosphorylase OH OH V
U~03~ -O - H~C ~ F
I Reductase H/ H2O3P-OH2C o HO OH /
\~
RNS HO
The abbreviations;-are defined as follows:
d = deoxy dTPM = d-thymidine monophosphate dTDP = d~thymidine diphosphate dTTP = d-thymidine triphosphate DNA = d-ribonucleic aeid The disadvantages of therapy with fluorouracil is precisely that fluorouracil is mainly built into the RNA and is available only in small amounts for conversion to the cytostatically active compound, fluorouracil deoxyriboside triphosphate.
To inc~ease the cytostatie effectiveness of 5~fluoro-uracil, the latter is administered in combination ~ith thymidine. Here thymine arises in the organism from the : i~853 thymidine, but however leads to toxic byproducts, since it is not excreted unchanged from the organ~sm but is decomposed and thus wastes importar.t enz:ymes~ This.decomposition of thymine is shown by the following reaction scheme:
HN~ ~CCH
N~
H
o HN~ ~CHCH 3 OC~ ~CH2 H DHT
o COH
H2N~ ~CHCH3 N~
H BUIB
o COH
H2N~ BAIB
The abbreviations are de~ined as follows:
DHT = dihydrothymine BUIB = ~-ureido-isobutyric acid B~IB = ~-amino~isobutyric acid This decomposition of thymine is a heav~ additional load for the organism, iZtSS3 S~ARY OF:THE INVENTION
.. . .
It has now been surprisingly found that 5-alkyl-pyrimidine nucleosides of the general for~ula I
o ~N~
N
O ~ (I) y-O-C~4 o~}
H
OH x where:
R = Alkyl with 2-10 C-Atoms;
x = H or OE;
o y =--~--Rl O O
O O
10 - C -CH- O -C -O -R1, C~I 3 where Rl = Cl-C6-Alkyl, straight-chain or branched, for example Methyl, Ethyl, Propyl, Butyl, Isobutyl, Pentyl or Hexyl, in particular Ethyl, Isopropyl or Isobutyl;
O
y = -C ~
- C -(CH2)n ~ R2, where R2 = -NH2, ~COO~I, n = 1-4, ~6ZF~S3 o - C -(CH2)n- CN, where n = 1-4 O Hal -C -C -Hal, where Hal = F or Cl, ~al O O
il 11 -C -(CH2~n- C -A, where n = 1-4 and A denotes a pyrimldine nucleoside of Formula:
o R
o~J
--OH2C~ o ~
HO X
in which R and Y, have the meanings stated above, where the y-residues can be esterified with the OH-group in the 3'-position if desired, instead of with the 5'-OH group, considerably increase the cytostatic action of fluorouracil~
Apart from this, they have a virostatic action.
Examples of suitable residues R are ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl residues, which can be straight-chain or branched.
The invention, in one aspect, is directed to a method for acco~plishing at least one of the following purposes, treat~ent of malignant diseases, i~unosuppressive therapy, cytostatic and virostatic action, which method comprises administering to a mammal, in need of such treatment, an effective amount of a 5-alkyl-pyrimidine nucleoside of the general formula I as defined above, The compound may be administered before, after or in combination with 5-fluorouracil, to a mammal requiring fluorouracil treatment. In another aspect, ~B53.
the invention relates to a medicament containing a compound of the formula I, alone or in combination with 5-~luorouracil, in a pharmaceutically compatible carrier or diluent.
DETAILED DESCRIPTION
The compounds described here can ~e produced analogously to the process of DE--OS 2,807,588, in which a nucleoside of the general formula II:
\ ~
O ~ N~ II
~3 R
where R is as above and R3 stands for H or a conventional protective group, in particular for the acetyl or propionyl residue, is reacted with a functional carbonyl derivative, ~7hich is derived from one of the a~ove~de~ined residues of - formula y, in particular a halocarbonyl derivative of formula y-Cl, in a basic medium at a temperature between about 0C and room temperature.
As functional carbonyl derivative there can be used a conventional, easily transesterifiable ester.
Pyridine, triethylamine, or dimethyl formamide can be used as the base-~
The starting compounds of formula II can be prepared according to DE-OS 1,620,185.
The medicament is characteri~ed in that it contains at least one compound of general formula I in a conventional pharmaceutical carrier, such as used with 5~fluorouracil, and also if necessary other additivesO
The testing of the action of the compound according to the invention for cytostatic effectiveness was performed on Ehrlich ascites tumors and L1210 ~mouse leukemia~. The survival period or the inhibition of the ascites tumor were , ..
~ii21S~;~
-7~
taken as the measure for cytostatic effectiveness, The test compol~nds were administered intraperitoneally or subcutaneously.
The results of these investigations are collected in the following table:
TABLE
Tumor, Ehrlich Ascites ~ Beginning of Treatment 6 Days Post-Inoculation, Application: suhcutaneous, Substance Dose Tumor Surviving No~ of ani- Mouse mg/kg wt,,g mice of 6 tumor or tu- Strain mo~r below lg .
Piv-~x-du20012.04 5 - BALB
Piv-Hx-du2003.20 4 + Fu 5 Fu 514,43 5 Piv-ADU 20013,48 6 Control 12~84 5 Piv-Hx-du = 5'-pivaloyl-5-hexyl-deoxyuridine Piv-ADU = 5'-pivaloyl-5-ethyl-deoxyuridine FU = 5-fluorouracil The data in the table show the effects on the already developed tumors. Treatment was begun on the 6th day after inoculation and continued until the 10th day (total of 5 treatments), The combination Piv-~-du ~200 mg/kg) and FU (5 mg/
kg) led to the surprising result that the tumor weight was reduced from 12.84 g to 3.2 g, although each component was inef~ective on its own.
The administration of the substances according to the invention can be effected orally or parentally in combination with a conventional, pharmaceutically compatible diluent or carrier, such as used with 5-fluorouracil, and in fact can ~e administered before, at the time of, or after ~16~;3 the administration of the fluorouracil. One aspect of the present invention is thus also a new medicament which contains fluorouracil in combination with 5-alkyl-pyrimidine nucleo-sides in a pharmaceutically compatible carrier or diluent.
Production Ex'ample 5-etnyl-2'-deoxyuridine-5~-O--pivaloate A solution of 25,8 g ~0.1 moll of 5-ethyl-2~-deoxy~
uridine in 150 ml of dry pyridine is dropped slowly, with stirring and cooling in an ice bath, into a solution of 12 g ~0.1 mol) of pivaloyl chloride in 80 ml of pyridine. The reaction solution is stirred for 4 hours at room temperature then the mixture is concentrated in vacuum and the residue is taken up in methylene chloride. This solution is extracted first with 1% aqueous sulfuric acid and then with 5% aqueous sodium carbonate solution, The methylene chloride solution is dried over sodium sulfate and then concentrated. The residue is purified on a silica gel column, using chloroform/
methanol (98/2~. Thin layer homogeneous fractions are collected and concentrated~ The desired product is obtained in pure form, Yield 19.5 g. Melting point: 181C (after temporary melting).
In the same way, there is obtained from 5n-hexyl-
5-Fluorouracil is known as a cytostatically active substance. According to present knowledge, it is converted in the organism to fluorouracil riboside monophosphate and in major part built into the RNA. Only a small fraction of the fluorouracil riboside monophosphate is transformed into 5-fluorouracil deoxy-riboside monophosphate by the action of the enzyme pyridine nucleotide reductase and then phosphorylated into the corresonding triphosphate. For cytostatic action, it is known that fluorouracil deoxyriboside triphosphate is responsible. Namely, it is a strong inhibitor of thymidilate kinase and thus inhibits DNA synthesis.
This process is schematically shown below.
- -;; ~16~
~ ~ dT~lP-~ dTDP ~__dTTP --~DNS
O ~ N ~ ~
(FU = Fluorouracil) O O O ~ N
Nucleoside H2O3P-O-P-O-PI-O-cH2 phosphorylase OH OH V
U~03~ -O - H~C ~ F
I Reductase H/ H2O3P-OH2C o HO OH /
\~
RNS HO
The abbreviations;-are defined as follows:
d = deoxy dTPM = d-thymidine monophosphate dTDP = d~thymidine diphosphate dTTP = d-thymidine triphosphate DNA = d-ribonucleic aeid The disadvantages of therapy with fluorouracil is precisely that fluorouracil is mainly built into the RNA and is available only in small amounts for conversion to the cytostatically active compound, fluorouracil deoxyriboside triphosphate.
To inc~ease the cytostatie effectiveness of 5~fluoro-uracil, the latter is administered in combination ~ith thymidine. Here thymine arises in the organism from the : i~853 thymidine, but however leads to toxic byproducts, since it is not excreted unchanged from the organ~sm but is decomposed and thus wastes importar.t enz:ymes~ This.decomposition of thymine is shown by the following reaction scheme:
HN~ ~CCH
N~
H
o HN~ ~CHCH 3 OC~ ~CH2 H DHT
o COH
H2N~ ~CHCH3 N~
H BUIB
o COH
H2N~ BAIB
The abbreviations are de~ined as follows:
DHT = dihydrothymine BUIB = ~-ureido-isobutyric acid B~IB = ~-amino~isobutyric acid This decomposition of thymine is a heav~ additional load for the organism, iZtSS3 S~ARY OF:THE INVENTION
.. . .
It has now been surprisingly found that 5-alkyl-pyrimidine nucleosides of the general for~ula I
o ~N~
N
O ~ (I) y-O-C~4 o~}
H
OH x where:
R = Alkyl with 2-10 C-Atoms;
x = H or OE;
o y =--~--Rl O O
O O
10 - C -CH- O -C -O -R1, C~I 3 where Rl = Cl-C6-Alkyl, straight-chain or branched, for example Methyl, Ethyl, Propyl, Butyl, Isobutyl, Pentyl or Hexyl, in particular Ethyl, Isopropyl or Isobutyl;
O
y = -C ~
- C -(CH2)n ~ R2, where R2 = -NH2, ~COO~I, n = 1-4, ~6ZF~S3 o - C -(CH2)n- CN, where n = 1-4 O Hal -C -C -Hal, where Hal = F or Cl, ~al O O
il 11 -C -(CH2~n- C -A, where n = 1-4 and A denotes a pyrimldine nucleoside of Formula:
o R
o~J
--OH2C~ o ~
HO X
in which R and Y, have the meanings stated above, where the y-residues can be esterified with the OH-group in the 3'-position if desired, instead of with the 5'-OH group, considerably increase the cytostatic action of fluorouracil~
Apart from this, they have a virostatic action.
Examples of suitable residues R are ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl residues, which can be straight-chain or branched.
The invention, in one aspect, is directed to a method for acco~plishing at least one of the following purposes, treat~ent of malignant diseases, i~unosuppressive therapy, cytostatic and virostatic action, which method comprises administering to a mammal, in need of such treatment, an effective amount of a 5-alkyl-pyrimidine nucleoside of the general formula I as defined above, The compound may be administered before, after or in combination with 5-fluorouracil, to a mammal requiring fluorouracil treatment. In another aspect, ~B53.
the invention relates to a medicament containing a compound of the formula I, alone or in combination with 5-~luorouracil, in a pharmaceutically compatible carrier or diluent.
DETAILED DESCRIPTION
The compounds described here can ~e produced analogously to the process of DE--OS 2,807,588, in which a nucleoside of the general formula II:
\ ~
O ~ N~ II
~3 R
where R is as above and R3 stands for H or a conventional protective group, in particular for the acetyl or propionyl residue, is reacted with a functional carbonyl derivative, ~7hich is derived from one of the a~ove~de~ined residues of - formula y, in particular a halocarbonyl derivative of formula y-Cl, in a basic medium at a temperature between about 0C and room temperature.
As functional carbonyl derivative there can be used a conventional, easily transesterifiable ester.
Pyridine, triethylamine, or dimethyl formamide can be used as the base-~
The starting compounds of formula II can be prepared according to DE-OS 1,620,185.
The medicament is characteri~ed in that it contains at least one compound of general formula I in a conventional pharmaceutical carrier, such as used with 5~fluorouracil, and also if necessary other additivesO
The testing of the action of the compound according to the invention for cytostatic effectiveness was performed on Ehrlich ascites tumors and L1210 ~mouse leukemia~. The survival period or the inhibition of the ascites tumor were , ..
~ii21S~;~
-7~
taken as the measure for cytostatic effectiveness, The test compol~nds were administered intraperitoneally or subcutaneously.
The results of these investigations are collected in the following table:
TABLE
Tumor, Ehrlich Ascites ~ Beginning of Treatment 6 Days Post-Inoculation, Application: suhcutaneous, Substance Dose Tumor Surviving No~ of ani- Mouse mg/kg wt,,g mice of 6 tumor or tu- Strain mo~r below lg .
Piv-~x-du20012.04 5 - BALB
Piv-Hx-du2003.20 4 + Fu 5 Fu 514,43 5 Piv-ADU 20013,48 6 Control 12~84 5 Piv-Hx-du = 5'-pivaloyl-5-hexyl-deoxyuridine Piv-ADU = 5'-pivaloyl-5-ethyl-deoxyuridine FU = 5-fluorouracil The data in the table show the effects on the already developed tumors. Treatment was begun on the 6th day after inoculation and continued until the 10th day (total of 5 treatments), The combination Piv-~-du ~200 mg/kg) and FU (5 mg/
kg) led to the surprising result that the tumor weight was reduced from 12.84 g to 3.2 g, although each component was inef~ective on its own.
The administration of the substances according to the invention can be effected orally or parentally in combination with a conventional, pharmaceutically compatible diluent or carrier, such as used with 5-fluorouracil, and in fact can ~e administered before, at the time of, or after ~16~;3 the administration of the fluorouracil. One aspect of the present invention is thus also a new medicament which contains fluorouracil in combination with 5-alkyl-pyrimidine nucleo-sides in a pharmaceutically compatible carrier or diluent.
Production Ex'ample 5-etnyl-2'-deoxyuridine-5~-O--pivaloate A solution of 25,8 g ~0.1 moll of 5-ethyl-2~-deoxy~
uridine in 150 ml of dry pyridine is dropped slowly, with stirring and cooling in an ice bath, into a solution of 12 g ~0.1 mol) of pivaloyl chloride in 80 ml of pyridine. The reaction solution is stirred for 4 hours at room temperature then the mixture is concentrated in vacuum and the residue is taken up in methylene chloride. This solution is extracted first with 1% aqueous sulfuric acid and then with 5% aqueous sodium carbonate solution, The methylene chloride solution is dried over sodium sulfate and then concentrated. The residue is purified on a silica gel column, using chloroform/
methanol (98/2~. Thin layer homogeneous fractions are collected and concentrated~ The desired product is obtained in pure form, Yield 19.5 g. Melting point: 181C (after temporary melting).
In the same way, there is obtained from 5n-hexyl-
2'-deoxyuridine, 5-n-hexyl-2'-deoxyuridine-5'-O-pivaloate with melting point 143C, in 65% yield.
The other compounds used according to the invention can be produced in an analogous manner.
The other compounds used according to the invention can be produced in an analogous manner.
Claims (3)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A composition for the treatment of malignant disease or for immunosupp-ressive therapy, cytostatic and virostatic action, comprising an effective amount of a 5-alkyl-pyrimidine nucleoside of the general formula I:
(I) where:
R = alkyl with 2-10 C-Atoms;
x = H or OH;
y = _?_R1, where R1 = C1-C6-alkyl, straight-chain or branched, for example methyl, ethyl, propyl, butyl, isobutyl, pentyl or hexyl;
, where R2 = -NH2, -COOH, n = 1-4, -C-(CH2) -CN, where n = 1-4 where Hal = F or Cl, Ol o ( 2)n ~ where n = 1-4 and A denotes a pyrimidine nucleoside of the Formula:
in which R and X have the meanings stated above, in which the y-residues can be esterified if desired with the OH group in the 3'-position instead of with the 5'-OH-group, together with a pharmaceutically compa-tible carrier or diluent.
(I) where:
R = alkyl with 2-10 C-Atoms;
x = H or OH;
y = _?_R1, where R1 = C1-C6-alkyl, straight-chain or branched, for example methyl, ethyl, propyl, butyl, isobutyl, pentyl or hexyl;
, where R2 = -NH2, -COOH, n = 1-4, -C-(CH2) -CN, where n = 1-4 where Hal = F or Cl, Ol o ( 2)n ~ where n = 1-4 and A denotes a pyrimidine nucleoside of the Formula:
in which R and X have the meanings stated above, in which the y-residues can be esterified if desired with the OH group in the 3'-position instead of with the 5'-OH-group, together with a pharmaceutically compa-tible carrier or diluent.
2. A composition according to claim 1, wherein a compound of formula I is employed in which R is ethyl, isopropyl or isobutyl.
3. A composition according to claim 1 or 2, and also containing 5-fluoro-uracil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803010397 DE3010397A1 (en) | 1980-03-18 | 1980-03-18 | USE OF 5-ALKYL-PYRIMIDINE NUCLEOSIDES AS A CYTOSTATIKA |
| DEP3010397.0 | 1980-03-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1162853A true CA1162853A (en) | 1984-02-28 |
Family
ID=6097574
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000373253A Expired CA1162853A (en) | 1980-03-18 | 1981-03-18 | Medicaments containing 5-alkyl-pyrimidine nucleosides and use as cytostatic and virostatic agents |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS56140921A (en) |
| CA (1) | CA1162853A (en) |
| CH (1) | CH655934A5 (en) |
| DE (1) | DE3010397A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4880785A (en) * | 1987-08-07 | 1989-11-14 | Mta Kozponti Kemiai Kutato Intezete And Biogal Gyogyszergyar | Topical process for treating herpes infections using 5-isopropyl-2'-β-d |
| US5268365A (en) * | 1988-03-11 | 1993-12-07 | Rudolph Frederick B | Nucleotides, nucleosides, and nucleobases in immune function restoration enhancement or maintenance |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58152898A (en) * | 1982-03-08 | 1983-09-10 | Taiho Yakuhin Kogyo Kk | 2'-deoxy-5-trifluoromethyluridine derivative, its preparation and antitumor agent containing the same |
| ATA173599A (en) * | 1999-10-14 | 2001-04-15 | Lilly Co Eli | PHARMACEUTICAL PRODUCT |
-
1980
- 1980-03-18 DE DE19803010397 patent/DE3010397A1/en not_active Withdrawn
-
1981
- 1981-03-12 JP JP3642881A patent/JPS56140921A/en active Pending
- 1981-03-12 CH CH1693/81A patent/CH655934A5/en not_active IP Right Cessation
- 1981-03-18 CA CA000373253A patent/CA1162853A/en not_active Expired
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4880785A (en) * | 1987-08-07 | 1989-11-14 | Mta Kozponti Kemiai Kutato Intezete And Biogal Gyogyszergyar | Topical process for treating herpes infections using 5-isopropyl-2'-β-d |
| AU605875B2 (en) * | 1987-08-07 | 1991-01-24 | Biogal Gyogyszergyar | Externally applicable, antiviral pharmaceutical composition accumulating in the skin and process for the preparation of same |
| US5268365A (en) * | 1988-03-11 | 1993-12-07 | Rudolph Frederick B | Nucleotides, nucleosides, and nucleobases in immune function restoration enhancement or maintenance |
Also Published As
| Publication number | Publication date |
|---|---|
| CH655934A5 (en) | 1986-05-30 |
| JPS56140921A (en) | 1981-11-04 |
| DE3010397A1 (en) | 1981-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dyson et al. | The synthesis and antiviral activity of some 4'-thio-2'-deoxy nucleoside analogs | |
| US6153594A (en) | 5'-O-acylated antiviral nucleosides | |
| DE69634747T2 (en) | Aryl-ester phosphoramidate derivatives of 2 ', 3'-didehydronucleosides | |
| US6573247B1 (en) | Anti-viral pyrimidine nucleoside analogues | |
| EP2955190B1 (en) | Chemical compounds | |
| DE69318836T2 (en) | 1,5-ANHYDROHEXITOL NUCLEOSIDE ANALOG AND PHARMACEUTICAL USE THEREOF | |
| Mikhailopulo et al. | Synthesis and antiviral and cytostatic properties of 3'-deoxy-3'-fluoro-and 2'-azido-3'-fluoro-2', 3'-dideoxy-D-ribofuranosides of natural heterocyclic bases | |
| CS246075B2 (en) | Method of 2,2-difluoronucleoside production | |
| KR100272732B1 (en) | Acyl derivatives of nucleosides and nucleoside analogues having anti-viral activity and pharmaceutical compositions containing them | |
| US6372725B1 (en) | Specific lipid conjugates to nucleoside diphosphates and their use as drugs | |
| CA1162853A (en) | Medicaments containing 5-alkyl-pyrimidine nucleosides and use as cytostatic and virostatic agents | |
| DE69403588T2 (en) | 4-ETHOXY-5-FLUOR-2'-DEOXYURIDINE | |
| JP4879398B2 (en) | Glyceryl nucleotides, their production and use | |
| RU2347786C2 (en) | Derivatives of ester nucleotide lipids | |
| US4730001A (en) | Carbocyclic analogues of amino and azido thymidines | |
| Villard et al. | An original pronucleotide strategy for the simultaneous delivery of two bioactive drugs | |
| SANEYOSHI et al. | Synthetic nucleosides and nucleotides. XVIII. Synthesis and cytostatic activity of 5-fluoropyrimidine nucleosides of 3-amino-3-deoxy-β-D-ribofuranose and related compounds | |
| Bobek et al. | 2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides | |
| US5574021A (en) | Methods of treatment using 2',3'-dideoxy-2',2'-difluoronucleosides | |
| SU961354A1 (en) | 3-flucrine-2,3-didesoxyadenozin showing cytostatic activity | |
| Jeong et al. | Synthesis of a 2, 3-dideoxy-2, 3-difluorofuranose with the D-lyxo configuration. An intramolecular rearrangement of methyl 5-O-benzoyl-2, 3-dideoxy-2, 3-difluoro-D-lyxofuranoside observed during the attempted synthesis of 1-(2, 3-dideoxy-2, 3-difluoro-β-D-lyxofuranosyl) thymine | |
| WO2012016994A1 (en) | Bone-targeting bisphosphonate duplex drugs | |
| Smee et al. | Synthesis and Anti-Herpetic Activity of A 2′-Fluoroarabinosyl Analog of Trifluridine | |
| Mikhailopulo et al. | Synthesis and biological properties of 2-amino-3-fluoro-2, 3-dideoxy-D-pentofuranosides of natural heterocyclic bases | |
| KR100730768B1 (en) | 5'-deoxy-N-alkyloxycarbonyl-5-fluorocytosine-5'-carboxylic acid and its derivatives, and process for preparing thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |