Pyrrolo[1,2-
Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds.
1. A compound of Formula (II):
or a pharmaceutically acceptable salt thereof;
wherein:
R 3 is F;
R 4 is CN;
R 5 is
wherein:
n′ is selected from 1, 2, 3, and 4;
R 8 is selected from C 1 -C 8 alkyl, —O—C 1 -C 8 alkyl, benzyl, —O-benzyl, —CH 2 —C 3 -C 6 cycloalkyl, —O—CH 2 —C 3 -C 6 cycloalkyl, and CF 3 ;
R 9 is phenyl;
R 10 is selected from H and CH 3 ;
R 11 is selected from H or C 1 -C 6 alkyl;
R 12 is selected from H, C 1 -C 8 alkyl, benzyl, C 3 -C 6 cycloalkyl, and CH 2 —C 3 -C 6 cycloalkyl.
2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof,
wherein R 5 is
wherein:
R 8 is selected from C 1 -C 8 alkyl, —O—C 1 -C 8 alkyl, benzyl, and —CH 2 —C 3 -C 6 cycloalkyl; and
R 12 is selected from C 1 -C 8 alkyl, benzyl, C 3 -C 6 cycloalkyl, and —CH 2 —C 3 -C 6 cycloalkyl.
3. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 8 and R 9 are each C 1 -C 8 alkyl.
4. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 8 and R 9 are each selected from C 1 -C 6 alkyl.
5. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 8 and R 9 are each selected from C 1 -C 4 alkyl.
6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from:
7. A method of treating Pneumovirinae virus infection in a human, the method comprising administering to the human a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 wherein the Pneumovirinae virus infection in a human is a human respiratory syncytial virus infection.
9. A pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.