Nucleoside phosphoramidate prodrugs
View Patent ↗Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.
1. (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid isopropyl ester or a stereoisomer thereof.
2. A composition comprising the compound or a stereoisomer thereof as claimed in claim 1 and a pharmaceutically acceptable medium.
3. A composition for treating a hepatitis C virus, which comprises an effective amount of the compound or a stereoisomer thereof as claimed in claim 1 and a pharmaceutically acceptable medium.
4. A method of treating a subject infected by a virus, which comprises:
administering to the subject an effective amount of the compound or a stereoisomer thereof as claimed in claim 1 ;
wherein the virus is selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus.
5. A method of treating a hepatitis C virus infection in a subject in need thereof, which comprises:
administering to the subject an effective amount of the compound or a stereoisomer thereof as claimed in claim 1 .
6. A process for preparing the compound or a stereoisomer thereof as claimed in claim 1 , said process comprising:
reacting a compound 4″ with a nucleoside analog 5′
wherein X′ is a leaving group.
7. A product comprising the compound or a stereoisomer thereof as claimed in claim 1 obtained by a process comprising:
reacting a compound 4″ with a nucleoside analog 5′
wherein X′ is a leaving group.
8. (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate.
9. A composition comprising the compound as claimed in claim 8 and a pharmaceutically acceptable medium.
10. A composition for treating a hepatitis C virus, which comprises an effective amount of the compound as claimed in claim 8 and a pharmaceutically acceptable medium.
11. A method of treating a subject infected by a virus, which comprises:
administering to the subject an effective amount of the compound as claimed in claim 8 ;
wherein the virus is selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus.
12. A method of treating a hepatitis C virus infection in a subject in need thereof, which comprises:
administering to the subject an effective amount of the compound as claimed in claim 8 .
13. A process for preparing the compound as claimed in claim 8 , said process comprising:
reacting a compound 4″ with a nucleoside analog 5′
wherein X′ is a leaving group.
14. A product comprising the compound as claimed in claim 8 obtained by a process comprising:
reacting a compound 4″ with a nucleoside analog 5′
wherein X′ is a leaving group.