TOLL LIKE RECEPTOR MODULATOR COMPOUNDS

• US 20180086755A1
• Filed: 08/31/2017
• Published: 03/29/2018
• Est. Priority Date: 09/02/2016
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Chin, Gregory, Mackman, Richard L., Mish, Michael R., Zablocki, Jeff
• Granted Patent: US 10,640,499 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

This application relates generally to toll like receptor modulator compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR8), and methods of making and using them.

Claims

1. A compound, which is

2. The compound of claim 1, which is

3. The compound of claim 1, which is

4. The compound of claim 1, which is

5. The compound of claim 1, which is

6. The compound of claim 1, which is

7. The compound of claim 1, which is

8. The compound of claim 1, which is

9. The compound of claim 1, which is

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

11. The pharmaceutical composition of claim 10, further comprising one or more additional therapeutic agents.

12. The pharmaceutical composition of claim 11, wherein one or more additional agents are selected from the group consisting of HBV DNA polymerase inhibitors, toll-like receptor 7 modulators, toll-like receptor 8 modulators, toll-like receptor 7 and 8 modulators, toll-like receptor 3 modulators, interferon alpha ligands, HBsAg inhibitors, compounds targeting HbcAg, cyclophilin inhibitors, HBV therapeutic vaccines, HBV prophylactic vaccines, HBV viral entry inhibitors, NTCP inhibitors, antisense oligonucleotide targeting viral mRNA, short interfering RNAs (siRNA), hepatitis B virus E antigen inhibitors, HBx inhibitors, cccDNA inhibitors, HBV antibodies including HBV antibodies targeting the surface antigens of the hepatitis B virus, thymosin agonists, cytokines, nucleoprotein inhibitors (HBV core or capsid protein inhibitors), stimulators of retinoic acid-inducible gene 1, stimulators of NOD2, recombinant thymosin alpha-1 and hepatitis B virus replication inhibitors, hepatitis B surface antigen (HBsAg) secretion or assembly inhibitors, IDO inhibitors, and combinations thereof.

13. The pharmaceutical composition of claim 11, wherein one or more additional therapeutic agents are selected from the group consisting of entecavir, adefovir, tenofovir disoproxil fumarate, tenofovir alafenamide, tenofovir, tenofovir disoproxil, tenofovir alafenamide fumarate, tenofovir alafenamide hemifumarate, telbivudine and lamivudine.

14. The pharmaceutical composition of claim 11, wherein one or more additional therapeutic agents are selected from HIV protease inhibitors, HIV non-nucleoside or non-nucleotide inhibitors of reverse transcriptase, HIV nucleoside or nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, HIV non-catalytic site (or allosteric) integrase inhibitors, pharmacokinetic enhancers, and combinations thereof.

15. A method of modulating TLR8, comprising administering a compound of claim 1, or a pharmaceutically acceptable salt thereof, to a human.

16. A method of treating or preventing a disease or condition responsive to the modulation of TLR8, comprising administering to a human a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

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

19. The method of claim 18, wherein the viral infection is a hepatitis B viral infection.

23. The method of claim 18, wherein the viral infection is a HIV infection.

27. A method of treating a hyperproliferative disease, comprising administering to an individual in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

31. A kit comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof.

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