2′-chloro aminopyrimidinone and pyrimidine dione nucleosides
Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds.
1. A method of treating Pneumovirinae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of Formula (II) or Formula (III), or a pharmaceutically acceptable salt thereof:
wherein
R 3 is H or F;
R 5 is selected from the group consisting of CN; unsubstituted C 1 -C 4 alkyl; C 1 -C 4 alkyl substituted with 1, 2, or 3 halogens; C 1 -C 4 alkyl substituted with 1 substituent selected from —S—CH 3 and —O—CH 3 ; C 2 -C 4 alkenyl; C 2 -C 4 alkynyl; unsubstituted C 3 -C 6 cycloalkyl; and C 3 -C 6 cycloalkyl substituted by 1, 2, or 3 substituents selected from F and CH 3 ;
R 4′ is H; and
R 4 is H,
2. The method of claim 1 , wherein R 5 is selected from the group of CN; unsubstituted C 1 -C 3 alkyl; C 1 -C 3 alkyl substituted with 1, 2, or 3 halogens selected from F and Cl; C 1 -C 3 alkyl substituted with 1 substituent selected from —S—CH 3 and —O—CH 3 ; C 2 -C 3 alkenyl; C 2 -C 3 alkynyl; unsubstituted C 3 -C 5 cycloalkyl; and C 3 -C 5 cycloalkyl substituted by 1, 2, or 3 substituents selected from F and CH 3 .
3. The method of claim 1 , wherein R 3 is hydrogen.
4. The method of claim 1 , wherein R 3 is F.
5. The method of claim 1 , wherein R 3 , R 4 , and R 4′ are each hydrogen.
6. The method of claim 1 , wherein R 3 is F and R 4 and R 4′ are each hydrogen.
7. The method of claim 1 , wherein R 5 is CN, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, CH 2 F, CHF 2 , CH 2 Cl, CH 2 SMe, —CH 2 OMe, or cyclopropyl.
8. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
11. The method of claim 1 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
12. The method of claim 2 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
13. The method of claim 3 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
14. The method of claim 4 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
15. The method of claim 5 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
16. The method of claim 6 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
17. The method of claim 7 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
18. The method of claim 8 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
19. The method of claim 9 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.
20. The method of claim 10 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.