Piperidine derivatives and methods of treating hepatitis B infections
Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
1. A compound of Formula II:
or a pharmaceutically acceptable salt thereof;
wherein
X 1 is halo;
R 4 is H or C 1 -C 3 alkyl;
each R 1 is halo;
each R 2 is halo;
Cy is
R 22 and R 23 are, independently at each occurrence, H or halo;
m is 0;
x is 1; and
y is 1, 2, 3, or 4.
2. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.
3. A method of treating an HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a compound according to claim 1 .
4. The method of claim 3 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of a HBV polymerase inhibitor, interferon, viral entry inhibitor, viral maturation inhibitor, BAY 41-4109, reverse transcriptase inhibitor, a TLR-agonist, AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide), and AT-130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide), and a combination thereof.
5. The method of claim 3 , further comprising administering to the individual at least one HBV vaccine, a nucleoside HBV inhibitor, an interferon or any combination thereof.
6. A method of treating an HBV infection in an individual in need thereof, comprising reducing the HBV viral load by administering to the individual a therapeutically effective amount of a compound according to claim 1 , or a compound according to claim 1 in combination with a reverse transcriptase inhibitor; and further administering to the individual a therapeutically effective amount of HBV vaccine.
7. The method of claim 3 further comprising monitoring the HBV viral load of the subject, and wherein the method is carried out for a period of time such that the HBV virus is undetectable.
8. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.