Compounds for the treatment of hepatitis B virus infection

• US 10,442,804 B2
• Filed: 01/31/2018
• Issued: 10/15/2019
• Est. Priority Date: 02/02/2017
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Aktoudianakis, Evangelos, Canales, Eda, Currie, Kevin S., Kato, Darryl, Li, Jiayao, Link, John O., Metobo, Samuel E., Saito, Roland D., Schroeder, Scott D., Shapiro, Nathan, Tse, Winston C., Wu, Qiaoyin, Hu, Yunfeng Eric
• Primary Examiner(s): Jackson, Shawquia
• Application Number:
  US15/885,390
• Publication Number:
  US 20180251460A1
• Time in Patent Office: 622 Days
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 471/14 Ortho-condensed systems
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 498/14 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present disclosure generally relates to compounds and pharmaceutical compositions which may be used in methods of treating a hepatitis B virus infection.

Claims

1. A compound of Formula (I):

2. The compound of claim 1, wherein R² is selected from the group consisting of chloro, methoxy, ethoxy, methoxymethyl, —

OCH(CH₃)₂, OC(CH₃)₃, cyclopropyl, —

OCF₃, —

OCHF₂ and

3. The compound of claim 1, wherein R² is methoxymethyl, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1, wherein R³ is C_1-6 alkoxyC_1-6alkyl, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1, wherein R³ is

6. The compound of claim 1, wherein R¹ and R⁴ are both H, or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1, wherein R¹ and R⁴ are both H and R² is cyclopropyl or methoxymethyl, or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1, having Formula (Ic):

9. The compound of claim 1, wherein at least two R⁵ groups are methyl bound at the same carbon atom, or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1, wherein A is:

11. The compound of claim 1 selected from:

12. The compound of claim 1 selected from:

13. The compound of claim 1 selected from:

14. The compound of claim 1 having the formula:

15. The compound of claim 1 having the formula:

16. The compound of claim 1 having the formula:

17. The compound of claim 1 having the formula:

18. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 1, and a pharmaceutically acceptable excipient.

19. A method of treating or preventing an HBV infection comprising administering to an individual in need thereof a therapeutically effective amount of a compound or pharmaceutically acceptable salt of claim 1 to the individual.

20. The compound of claim 1 selected from: