COMPOUNDS FOR THE TREATMENT OF HEPATITIS B VIRUS INFECTION

• US 20180251460A1
• Filed: 01/31/2018
• Published: 09/06/2018
• 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
• Granted Patent: US 10,442,804 B2
• Time in Patent Office: 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):

3. 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

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

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

29. The compound of claim 1, wherein R³ is

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

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

33. The compound of claim 1, comprising Formula (Ic):

37. 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.

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

61. The compound of claim 1 selected from:

62. The compound of claim 1 selected from:

63. The compound of claim 1 selected from:

64. The compound of claim 1 having the formula:

65. The compound of claim 1 having the formula:

66. The compound of claim 1 having the formula:

67. The compound of claim 1 having the formula:

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

74. 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.

85. The compound of claim 1 selected from:

2. (canceled)

4-11. -11. (canceled)

13-23. -23. (canceled)

25-28. -28. (canceled)

32. (canceled)

34-36. -36. (canceled)

38. (canceled)

39. (canceled)

41-60. -60. (canceled)

69-73. -73. (canceled)

75-84. -84. (canceled)

86-102. -102. (canceled)