Synthesis of purine nucleosides
A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.
1. A compound or salt thereof having the structure:
wherein R 7 is C 1-6 alkyl or C 3-6 cycloalkyl and R 8 is —O(C 1-6 alkyl) or —O(C 3-6 cycloalkyl).
2. The compound or salt thereof of claim 1 , wherein R 7 is methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, or cyclopentyl and R 8 is methoxy, ethoxy, isopropyloxy, —O-cyclopropyl, —O-cyclobutyl, or —O-cyclopentyl.
3. A compound or salt thereof of claim 2 having the structure:
4. A compound or salt thereof of claim 2 having the structure:
5. A compound or salt thereof of claim 2 having the structure:
6. A compound having the structure:
in crystalline form.
7. A compound having the structure:
in crystalline form having an XRD with a 2θ-reflection(°) at about 12.2.
8. A compound having the structure:
having an orthorhombic crystalline form.
9. The compound of claim 8 having an FT-IR peak at about 999 cm −1 .
10. A pharmaceutical composition comprising an effective amount of the compound or salt thereof of claim 1 and a pharmaceutically acceptable medium.
11. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of at least one agent selected from an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, an HCV NS4A inhibitor, an HCV NS4B inhibitor, and an HCV NS5a inhibitor; and
a pharmaceutically acceptable medium.
12. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of at least one agent selected from an HCV NS3 protease inhibitor, an HCV NS5B inhibitor, and an HCV NS5a inhibitor; and
a pharmaceutically acceptable medium.
13. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of at least one agent selected from an HCV NS3 protease inhibitor and an HCV NS5B inhibitor; and
a pharmaceutically acceptable medium.
14. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of at least one agent selected from an HCV NS3 protease inhibitor and an HCV NS5a inhibitor; and
a pharmaceutically acceptable medium.
15. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of at least one agent selected from an HCV NS5B inhibitor, and an HCV NS5a inhibitor; and
a pharmaceutically acceptable medium.
16. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of an HCV NS3 protease inhibitor; and
a pharmaceutically acceptable medium.
17. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of an HCV NS5B inhibitor; and
a pharmaceutically acceptable medium.
18. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of an HCV NS4A inhibitor; and
a pharmaceutically acceptable medium.
19. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount of an HCV NS4B inhibitor; and
a pharmaceutically acceptable medium.
20. A composition comprising:
an effective amount of the compound or a salt thereof of claim 1 ;
an effective amount an HCV NS5a inhibitor; and
a pharmaceutically acceptable medium.
21. A method of treating hepatitis C virus infection in a subject in need thereof, which comprises administering to the subject an effective amount of the compound or salt thereof of claim 1 .
22. The method of claim 21 , wherein the subject is a human.
23. A method of treating a hepatitis C virus infection in a subject in need thereof, which comprises:
administering to the subject the composition as claimed in any one of claims 11 - 20 .
24. The method of claim 23 , wherein the subject is a human.