Bi- and monocyclic nucleoside analogs for treatment of hepatitis E
The present disclosure is directed toward bi- and monocyclic nucleoside analogs, and compositions comprising these compounds for use in the treatment of hepatitis E infections.
1 . A method for treating a hepatitis E virus (HEV) infection in a subject in need thereof, comprising administering a compound of formula (Ia) to the subject:
or a pharmaceutically acceptable salt thereof, wherein:
Base is (b-1) or (b-6):
R 1 is OH or F;
R 2 is OH;
R 3 is (f-1), (f-2) or (f-3):
R 4 is F;
R 5 is C 1-4 alkyl or C 3-6 cycloalkyl;
R 6 is C 1-4 alkyl or C 3-6 cycloalkyl; and
R 7 is C 1-4 alkyl.
2 . The method of claim 1 , wherein the compound is:
3 . The method of claim 1 , wherein the compound is:
4 . The method of claim 1 , wherein the hepatitis E infection is a chronic HEV infection.
5 . The method of claim 1 , wherein the HEV infection is of genotype 1, genotype 2 or genotype 3.
6 . The method of claim 1 , wherein the subject is a pregnant woman, an immune-compromised subject or immune-deficient subject.
7 . The method of claim 1 , wherein the compound is administered to the subject in a pharmaceutical composition.