CA2470255A1 - N4-acylcytosine nucleosides for treatment of viral infections - Google Patents
N4-acylcytosine nucleosides for treatment of viral infections Download PDFInfo
- Publication number
- CA2470255A1 CA2470255A1 CA002470255A CA2470255A CA2470255A1 CA 2470255 A1 CA2470255 A1 CA 2470255A1 CA 002470255 A CA002470255 A CA 002470255A CA 2470255 A CA2470255 A CA 2470255A CA 2470255 A1 CA2470255 A1 CA 2470255A1
- Authority
- CA
- Canada
- Prior art keywords
- dideoxy
- beta
- fluorocytidine
- didehydro
- fluoro
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention is directed to a method and composition of treating or preventing viral infections, in particular, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections, in human patients or other animals hosts, comprising the administration of N4-acyl-2',3'-dideoxy-cytidine of formula (I) or N4-acyl-2',3'-didehydro-2',3' dideoxy-cytidine (II), and pharmaceutically acceptable salts, prodrugs, and other derivatives thereof:
(see formula I)(see formula II)
(see formula I)(see formula II)
Claims (17)
1. A compound of formula (I) or (II):
or a pharmaceutically acceptable salt or prodrug thereof, wherein i) X is O, S, NR5, CH2, CHF or CF2;
ii) Y is CH2, CHF or CF2;
iii) R1 is chosen from hydrogen, halogen (F, Cl, Br, I), alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, CN, CF3, N3, NO2, aryl, heteroaryl and acyl;
iv) R2 is chosen from alkenyl, alkynyl, cycloalkyl, aminoalkyl, hydroxyalkyl, haloalkyl, thioalkyl, aryl, heteroaryl, and C6H4R6 where R6 is chosen from halogen (F, Cl, Br, I), CN, CF3, N3, NO2, alkyl, haloalkyl, aminoalkyl, alkoxy, thioalkyl, alkenyl, alkynyl, and aryl;
v) R3 and R3' are chosen independently from H, halogen (F, Cl, Br, I), CN, CF3, N3, NO2, alkyl, alkenyl, and alkynyl;
vi) R4 is H, phosphate, carbonyl substituted with alkyl, alkenyl, alkynyl, aryl, or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R3 and R3' are H or phosphate, sulfonate ester, a lipid, an amino acid, a peptide, or cholesterol; and vii) R5 is H, acyl, alkyl, alkenyl, alkynyl, or cycloalkyl.
or a pharmaceutically acceptable salt or prodrug thereof, wherein i) X is O, S, NR5, CH2, CHF or CF2;
ii) Y is CH2, CHF or CF2;
iii) R1 is chosen from hydrogen, halogen (F, Cl, Br, I), alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, CN, CF3, N3, NO2, aryl, heteroaryl and acyl;
iv) R2 is chosen from alkenyl, alkynyl, cycloalkyl, aminoalkyl, hydroxyalkyl, haloalkyl, thioalkyl, aryl, heteroaryl, and C6H4R6 where R6 is chosen from halogen (F, Cl, Br, I), CN, CF3, N3, NO2, alkyl, haloalkyl, aminoalkyl, alkoxy, thioalkyl, alkenyl, alkynyl, and aryl;
v) R3 and R3' are chosen independently from H, halogen (F, Cl, Br, I), CN, CF3, N3, NO2, alkyl, alkenyl, and alkynyl;
vi) R4 is H, phosphate, carbonyl substituted with alkyl, alkenyl, alkynyl, aryl, or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R3 and R3' are H or phosphate, sulfonate ester, a lipid, an amino acid, a peptide, or cholesterol; and vii) R5 is H, acyl, alkyl, alkenyl, alkynyl, or cycloalkyl.
2. A pharmaceutical composition that includes an effective HIV or HBV
treatment amount of a compound of claim 1 in a pharmaceutically acceptable carrier or diluent.
treatment amount of a compound of claim 1 in a pharmaceutically acceptable carrier or diluent.
3. A method for the treatment of a host infected with HIV that includes administering an effective amount of a compound of claim 1 or 17 in a pharmaceutically acceptable carrier.
4. A method for the treatment of a host infected with HBV that includes administering an effective amount of a compound of claim 1 or 17 in a pharmaceutically acceptable carrier.
5. A method for the treatment of a host infected with HIV that includes administering an effective amount of a compound of claim 1 or 17 in a pharmaceutically acceptable carrier in combination with another anti-HIV
agent.
agent.
6. A method for the treatment of a host infected with HBV that includes administering an effective amount of a compound of claim 1 or 17 in a pharmaceutically acceptable carrier in combination with another anti-HIV
agent.
agent.
7. A compound of claim 1 or 17 for use in the treatment of host infected with HIV.
8. A compound of claim 1 or 17 for use in the treatment of a host infected with HBV
infection.
infection.
9. The use of a compound of claim 1 or 17 in the manufacture of a medicament for the treatment of a host infected with HIV.
10. The use of a compound of claim 1 or 17 in the manufacture of a medicament for the treatment of a host infected with HBV.
11. The compound of claim 1, 7 or 8 selected from the group consisting of .beta.-D-N4-p-iodobenzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-fluoro-benzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-chlorobenzoyl-2',3'-dideoxy-5-fluoro-cytidine, .beta.-D N4-p-bromobenzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-ethyl-benzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-t-butylbenzoyl-2',3'-dideoxy-5-fluoro-cytidine.
12. The compound of claim 1, 7 or 8 selected from the group consisting of .beta.-D-N4-p-bromobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-fluorobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-chlorobenzoyl-2',3'-didehydro-2' 3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-iodobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-ethylbenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, and .beta.-D-N4-p-t-butylbenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine.
13. The method of claims 2 or 3 wherein the compound is selected from the group consisting of .beta.-D-N4-p-iodobenzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-fluoro-benzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-chlorobenzoyl-2',3'-dideoxy-5-fluoro-cytidine, .beta.-D-N4-p-bromobenzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-ethyl-benzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-t-butylbenzoyl-2',3'-dideoxy-5-fluoro-cytidine.
14. The method of claims 2 or 3 wherein the compound is selected from the group consisting of .beta.-D-N4-p-bromobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-fluorobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-chlorobenzoyl-2',3'-didehydro-2'3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-iodobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-ethylbenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, and .beta.-D-N4-p-t-butylbenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine.
15. The use of claims 9 or 10 wherein the compound is selected from the group consisting of .beta.-D-N4-p-iodobenzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-fluoro-benzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-chlorobenzoyl-2',3'-dideoxy-5-fluoro-cytidine, .beta.-D-N4-p-bromobenzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-ethyl-benzoyl-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-t-butylbenzoyl-2',3'-dideoxy-5-fluoro-cytidine.
16. The use of claims 9 or 10 wherein the compound is selected from the group consisting of .beta.-D-N4-p-bromobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-fluorobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-chlorobenzoyl-2',3'-didehydro-2'3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-iodobenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, .beta.-D-N4-p-ethylbenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, and .beta.-D-N4-p-t-butylbenzoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine.
17. A compound selected from the following, or its pharmaceutically acceptable salt or prodrug:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-iodobenzoyl)cytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-fluorobenzoyl)cytidine of the structure:
.beta.-D-N4-(4-chlorobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-(4-bromobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro N4-(3-fluorobenzoyl)cytidine of the structure:
.beta.-D-N4-(3-chlorobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
or a pharmaceutically acceptable salt or prodrug thereof.
In one preferred embodiment, the active compound is .beta.-D-N4-(3-bromobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-nitrobenzoyl)cytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-p-toluoylcytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(m-toluoyl)cytidine of the structure:
.beta.-D-2',3'-dideoxy-N4-(4-ethylbenzoyl)-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-propylbenzoyl)cytidine of the structure:
.beta.-D-N4-(4-tert-butylbenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(2-thiophenecarbonyl)cytidine of the structure:
.beta.-D-N4-(benzo-[b]-thiophene-2-carbonyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-(cyclohexane-carbonyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-(4-iodobenzoyl)cytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-(4-fluorobenzoyl)cytidine of the structure:
.beta.-D-N4-(4-chlorobenzoyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-(4-bromobenzoyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-p-anisoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-(3-nitrobenzoyl)cytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-p-toluoylcytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-m-toluoylcytidine of the structure:
.beta.-D-N4-(4-t-butylbenzoyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
or a pharmaceutically acceptable salt or prodrug thereof.
.beta.-D-N4-cyclopentanecarbonyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
or a pharmaceutically acceptable salt or prodrug thereof.
.beta.-D-N4-(cyclohexanecarbonyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-iodobenzoyl)cytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-fluorobenzoyl)cytidine of the structure:
.beta.-D-N4-(4-chlorobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-(4-bromobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro N4-(3-fluorobenzoyl)cytidine of the structure:
.beta.-D-N4-(3-chlorobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
or a pharmaceutically acceptable salt or prodrug thereof.
In one preferred embodiment, the active compound is .beta.-D-N4-(3-bromobenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-nitrobenzoyl)cytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-p-toluoylcytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(m-toluoyl)cytidine of the structure:
.beta.-D-2',3'-dideoxy-N4-(4-ethylbenzoyl)-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(4-propylbenzoyl)cytidine of the structure:
.beta.-D-N4-(4-tert-butylbenzoyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-dideoxy-5-fluoro-N4-(2-thiophenecarbonyl)cytidine of the structure:
.beta.-D-N4-(benzo-[b]-thiophene-2-carbonyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-(cyclohexane-carbonyl)-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-(4-iodobenzoyl)cytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-(4-fluorobenzoyl)cytidine of the structure:
.beta.-D-N4-(4-chlorobenzoyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-(4-bromobenzoyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-N4-p-anisoyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-(3-nitrobenzoyl)cytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-p-toluoylcytidine of the structure:
.beta.-D-2',3'-didehydro-2',3'-dideoxy-5-fluoro-N4-m-toluoylcytidine of the structure:
.beta.-D-N4-(4-t-butylbenzoyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
or a pharmaceutically acceptable salt or prodrug thereof.
.beta.-D-N4-cyclopentanecarbonyl-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
or a pharmaceutically acceptable salt or prodrug thereof.
.beta.-D-N4-(cyclohexanecarbonyl)-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine of the structure:
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34155501P | 2001-12-14 | 2001-12-14 | |
| US60/341,555 | 2001-12-14 | ||
| PCT/US2002/040081 WO2003063771A2 (en) | 2001-12-14 | 2002-12-13 | N4-acylcytosine nucleosides for treatment of viral iinfections |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2470255A1 true CA2470255A1 (en) | 2003-08-07 |
| CA2470255C CA2470255C (en) | 2012-01-17 |
Family
ID=23338072
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2470255A Expired - Fee Related CA2470255C (en) | 2001-12-14 | 2002-12-13 | N4-acylcytosine nucleosides for treatment of viral infections |
Country Status (10)
| Country | Link |
|---|---|
| US (6) | US7105527B2 (en) |
| EP (1) | EP1569652A4 (en) |
| JP (1) | JP2005519916A (en) |
| KR (1) | KR100978904B1 (en) |
| CN (1) | CN100560073C (en) |
| AU (2) | AU2002365234B2 (en) |
| BR (1) | BR0214944A (en) |
| CA (1) | CA2470255C (en) |
| MX (1) | MXPA04005779A (en) |
| WO (2) | WO2003063771A2 (en) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6790228B2 (en) * | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
| BR0110023A (en) | 2000-04-13 | 2003-12-30 | Pharmasset Ltd | Substituted 3'-or-2 'nucleoside derivatives for treatment of hepatitis virus infections |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| EP1294735A2 (en) * | 2000-05-26 | 2003-03-26 | Novirio Pharmaceuticals Limited | Methods and compositions for treating flaviviruses and pestiviruses |
| CN100560073C (en) * | 2001-12-14 | 2009-11-18 | 法玛塞特公司 | The N that is used for the treatment of viral infection 4-acyl group cytidine |
| CN101172993A (en) * | 2002-06-28 | 2008-05-07 | 埃迪尼克斯(开曼)有限公司 | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| KR20050035194A (en) * | 2002-06-28 | 2005-04-15 | 이데닉스 (케이만) 리미티드 | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| JP2006507235A (en) | 2002-08-01 | 2006-03-02 | フアーマセツト・インコーポレイテツド | Compounds having bicyclo [4.2.1] nonane system for the treatment of Flaviviridae virus infection |
| CN1849142A (en) * | 2002-11-15 | 2006-10-18 | 埃迪尼克斯(开曼)有限公司 | 2'-branched nucleosides and flaviviridae mutation |
| US7598373B2 (en) * | 2002-12-12 | 2009-10-06 | Idenix Pharmaceuticals, Inc. | Process for the production of 2-C-methyl-D-ribonolactone |
| CA2425031A1 (en) * | 2003-04-01 | 2004-10-01 | Smithkline Beecham Corporation | Pharmaceutical compositions |
| EP2345661A1 (en) | 2003-05-30 | 2011-07-20 | Pharmasset, Inc. | Modified fluorinated nucleoside analogues |
| US7741334B2 (en) * | 2004-04-01 | 2010-06-22 | Achillion Pharmaceuticals, Inc. | Low dose therapy for treating viral infections |
| CN101023094B (en) * | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | Preparation of alkyl-substituted 2-deoxy-2-fluoro-d-ribofuranosyl pyrimidines and purines and their derivatives |
| AU2005285045B2 (en) | 2004-09-14 | 2011-10-13 | Gilead Pharmasset Llc | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
| WO2006044968A2 (en) * | 2004-10-19 | 2006-04-27 | Achillion Pharmaceuticals, Inc. | Combination therapy for treating viral infections |
| US7968703B2 (en) * | 2005-03-07 | 2011-06-28 | Shire Canada Inc. | Process and methods for the preparation of optically active cis-2-hydroxymethyl-4- (cytosin-1'-yl)-1,3-oxathiolane or pharmaceutically acceptable salts thereof |
| EP1976382B1 (en) * | 2005-12-23 | 2013-04-24 | IDENIX Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| GB0623493D0 (en) | 2006-11-24 | 2007-01-03 | Univ Cardiff | Chemical compounds |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| SG172361A1 (en) | 2008-12-23 | 2011-07-28 | Pharmasset Inc | Nucleoside analogs |
| AR074897A1 (en) | 2008-12-23 | 2011-02-23 | Pharmasset Inc | NUCLEOSID PHOSPHORAMIDATES |
| AU2009329872B2 (en) | 2008-12-23 | 2016-07-07 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| TWI583692B (en) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | Nucleoside phosphoramidates |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| EP2752422B1 (en) | 2010-03-31 | 2017-08-16 | Gilead Pharmasset LLC | Stereoselective synthesis of phosphorus containing actives |
| US8563530B2 (en) | 2010-03-31 | 2013-10-22 | Gilead Pharmassel LLC | Purine nucleoside phosphoramidate |
| ES2716158T3 (en) | 2010-11-30 | 2019-06-10 | Gilead Pharmasset Llc | 2'-spiro-nucleotides for the treatment of hepatitis C |
| MD4589C1 (en) | 2011-09-16 | 2019-03-31 | Gilead Pharmasset Llc | Pharmaceutical composition comprising sofosbuvir and uses thereof for treating hepatitis C virus |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| CN103242400B (en) * | 2012-02-08 | 2016-06-08 | 河南师范大学 | There is 5-substituted pyrimidines nucleoside-thiazolidhybrid hybrid and its preparation method of HIV (human immunodeficiency virus)-resistant activity |
| NZ625087A (en) | 2013-01-31 | 2017-05-26 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| ES2900570T3 (en) | 2013-08-27 | 2022-03-17 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| RU2764767C2 (en) | 2015-03-06 | 2022-01-21 | Атеа Фармасьютикалс, Инк. | β-D-2ʹ-DEOXY-2ʹ-α-FLUORO-2ʹ-β-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR TREATMENT OF DISEASES CAUSED BY HCV |
| US10711029B2 (en) | 2016-07-14 | 2020-07-14 | Atea Pharmaceuticals, Inc. | Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| PL3512863T3 (en) | 2016-09-07 | 2022-04-04 | Atea Pharmaceuticals, Inc. | 2'-substituted-n6-substituted purine nucleotides for rna virus treatment |
| SG10202012214WA (en) | 2017-02-01 | 2021-01-28 | Atea Pharmaceuticals Inc | Nucleotide hemi-sulfate salt for the treatment of hepatitis c virus |
| WO2019200005A1 (en) | 2018-04-10 | 2019-10-17 | Atea Pharmaceuticals, Inc. | Treatment of hcv infected patients with cirrhosis |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US13660A (en) * | 1855-10-09 | Improvements | ||
| US3309359A (en) * | 1965-10-22 | 1967-03-14 | Hoffmann La Roche | N-mono-acyl-5-fluorocytosine derivatives and process |
| NL8202626A (en) | 1982-06-29 | 1984-01-16 | Stichting Rega V Z W | DERIVATIVES OF 9- (2-HYDROXYETHOXYMETHYL) GUANINE. |
| US4522811A (en) * | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| GB8719367D0 (en) * | 1987-08-15 | 1987-09-23 | Wellcome Found | Therapeutic compounds |
| ZA886890B (en) * | 1987-10-09 | 1989-05-30 | Hoffmann La Roche | Novel dideoxycytidine derivatives |
| US6350753B1 (en) * | 1988-04-11 | 2002-02-26 | Biochem Pharma Inc. | 2-Substituted-4-substituted-1,3-dioxolanes and use thereof |
| NL8901258A (en) | 1989-05-19 | 1990-12-17 | Stichting Rega V Z W | New 5-halo-2'-3'-di:deoxy-cytidine derivs. - useful as anti-retro-viral agents, esp. for treating HIV infections |
| DD293498A5 (en) | 1989-07-20 | 1991-09-05 | Zi Fuer Molekularbiologie Der Adw,De | METHOD FOR PRODUCING A MEDIUM FOR THE TREATMENT OR PROPHYLAXIS OF HEPATITE INFECTIONS IN HUMANS AND ANIMALS |
| JPH05310777A (en) | 1992-05-14 | 1993-11-22 | Yoshitomi Pharmaceut Ind Ltd | 2'-deoxy-2'-methylidynecytidine compound |
| TW254946B (en) * | 1992-12-18 | 1995-08-21 | Hoffmann La Roche | |
| TW374087B (en) * | 1993-05-25 | 1999-11-11 | Univ Yale | L-2',3'-dideoxy nucleotide analogs as anti-hepatitis B(HBV) and anti-HIV agents |
| TW574214B (en) | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
| US5703058A (en) * | 1995-01-27 | 1997-12-30 | Emory University | Compositions containing 5-fluoro-2',3'-didehydro-2',3'-dideoxycytidine or a mono-, di-, or triphosphate thereof and a second antiviral agent |
| GB9525606D0 (en) * | 1995-12-14 | 1996-02-14 | Iaf Biochem Int | Method and compositions for the synthesis of dioxolane nucleosides with - configuration |
| WO1998017281A1 (en) * | 1996-10-24 | 1998-04-30 | Vion Pharmaceuticals, Inc. | MONOPHOSPHATE PRODRUGS OF β-L-FD4C AND β-L-FddC AS POTENT ANTIVIRAL AGENTS |
| AU1412299A (en) * | 1997-11-25 | 1999-06-15 | Protarga, Inc. | Nucleoside analog compositions and uses thereof |
| EP1058686B1 (en) * | 1998-02-25 | 2006-11-02 | Emory University | 2'-fluoronucleosides |
| US20030013660A1 (en) * | 2000-10-13 | 2003-01-16 | Shire Biochem Inc. | Dioxolane analogs for improved inter-cellular delivery |
| KR101201552B1 (en) * | 2000-10-18 | 2012-11-15 | 파마셋 인코포레이티드 | Modified nucleosides for treatment of viral infections and abnormal cellular proliferation |
| CN100560073C (en) * | 2001-12-14 | 2009-11-18 | 法玛塞特公司 | The N that is used for the treatment of viral infection 4-acyl group cytidine |
-
2002
- 2002-12-13 CN CNB028278402A patent/CN100560073C/en not_active Expired - Fee Related
- 2002-12-13 US US10/318,511 patent/US7105527B2/en not_active Expired - Fee Related
- 2002-12-13 JP JP2003563467A patent/JP2005519916A/en active Pending
- 2002-12-13 BR BR0214944-3A patent/BR0214944A/en not_active Application Discontinuation
- 2002-12-13 MX MXPA04005779A patent/MXPA04005779A/en active IP Right Grant
- 2002-12-13 CA CA2470255A patent/CA2470255C/en not_active Expired - Fee Related
- 2002-12-13 EP EP02804833A patent/EP1569652A4/en not_active Withdrawn
- 2002-12-13 KR KR1020047009263A patent/KR100978904B1/en not_active IP Right Cessation
- 2002-12-13 WO PCT/US2002/040081 patent/WO2003063771A2/en active Application Filing
- 2002-12-13 AU AU2002365234A patent/AU2002365234B2/en not_active Ceased
- 2002-12-16 AU AU2002364730A patent/AU2002364730A1/en not_active Abandoned
- 2002-12-16 WO PCT/US2002/040090 patent/WO2003051306A2/en not_active Application Discontinuation
- 2002-12-16 US US10/320,350 patent/US6908924B2/en not_active Ceased
-
2006
- 2006-07-31 US US11/461,338 patent/US20070078080A1/en not_active Abandoned
-
2007
- 2007-06-21 US US11/821,076 patent/USRE42015E1/en not_active Expired - Fee Related
-
2008
- 2008-01-04 US US11/969,427 patent/US8114997B2/en not_active Expired - Fee Related
-
2012
- 2012-02-13 US US13/371,654 patent/US20120202766A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN100560073C (en) | 2009-11-18 |
| EP1569652A4 (en) | 2008-07-02 |
| CA2470255C (en) | 2012-01-17 |
| US8114997B2 (en) | 2012-02-14 |
| WO2003063771A3 (en) | 2005-07-07 |
| US20070078080A1 (en) | 2007-04-05 |
| KR100978904B1 (en) | 2010-08-31 |
| US20120202766A1 (en) | 2012-08-09 |
| US20040214844A1 (en) | 2004-10-28 |
| KR20040094398A (en) | 2004-11-09 |
| AU2002365234B2 (en) | 2009-01-29 |
| US6908924B2 (en) | 2005-06-21 |
| MXPA04005779A (en) | 2005-05-16 |
| BR0214944A (en) | 2005-06-07 |
| AU2002364730A8 (en) | 2003-06-30 |
| CN1617726A (en) | 2005-05-18 |
| US20090176730A1 (en) | 2009-07-09 |
| AU2002364730A1 (en) | 2003-06-30 |
| WO2003051306A2 (en) | 2003-06-26 |
| EP1569652A2 (en) | 2005-09-07 |
| US20030176319A1 (en) | 2003-09-18 |
| USRE42015E1 (en) | 2010-12-28 |
| WO2003051306A3 (en) | 2003-12-18 |
| WO2003063771A2 (en) | 2003-08-07 |
| JP2005519916A (en) | 2005-07-07 |
| US7105527B2 (en) | 2006-09-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2470255A1 (en) | N4-acylcytosine nucleosides for treatment of viral infections | |
| JP2005519916A5 (en) | ||
| MXPA05005379A (en) | Substituted aryl thioureas and releated compounds; inhibitors of viral replication. | |
| WO2005067900A3 (en) | Azabenzofuran substituted thioureas as inhibitors of viral replication | |
| TW200600492A (en) | Substituted aryl acylthioureas and related compounds; inhibitors of viral replication | |
| WO2005095345A3 (en) | Heteroaryl guanidines as inhibitors of viral replication | |
| WO2006122011A3 (en) | Thiazole compounds and methods of use | |
| ZA200400925B (en) | Novel virus proliferation inhibition/virucidal method and novel pyradine nucleotide/pyradine nucleoside analogue | |
| JP2009535352A5 (en) | ||
| MEP26208A (en) | 4`-supstituted nucleosides | |
| CA2389745A1 (en) | Method for the treatment or prevention of flaviviridae viral infection using nucleoside analogues | |
| MY128463A (en) | 4' substituted nucleosides for the treatment of diseases mediated by the hepatitis c virus | |
| RU2008127750A (en) | ANTI-VIRUS NUCLEOSIDES | |
| RU2004100302A (en) | AMRIDES OF ANTHRANILIC ACID WITH A HETEROARYL SULPHONILY LATERAL CHAIN, METHOD FOR PRODUCING THEM, THEIR APPLICATION AS A MEDICINAL OR DIAGNOSTIC MEDICINE, AND ALSO CONTAINED | |
| RU2009141187A (en) | Sulfur-containing compounds as inhibitors of the NS3 seroprotease of the hepatitis C virus | |
| PL409123A1 (en) | Compounds, their use and compositions for the treatment of hepatitis C. | |
| RU2002120922A (en) | Nucleoside analogues with carboxamidine-modified monocyclic base | |
| DK1487829T3 (en) | Thiadizolylpiperazine derivatives useful for treating or preventing pain | |
| EA200700362A1 (en) | CONJUGAT, CONTAINING ANTI-VIRUS COMPOUND, IN PARTICULAR INHIBITING HIV, PHARMACEUTICAL COMPOSITION AND SET OF STANDARD DOSE OF THE MEDICINAL DRUG ON ITS BASIS, METHOD OF INHIBITING THE SOFTWARE PRO. | |
| JPH06500078A (en) | TNF inhibitor | |
| RU2011111117A (en) | TREATMENT OF AUTOIMMUNE DISEASES | |
| JP2002533470A5 (en) | ||
| ES2105923A1 (en) | Compositions containing 5-iodouracil derivatives for the treatment of hepatitis B infections. | |
| JP2005507944A5 (en) | ||
| HRP960045A2 (en) | Combination therapy for hiv infection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20141215 |