Substituted pyrrolizine compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-10328053-B2
Application number	US-201715686499-A
Country	US
Kind code	B2
Filing date	Aug 25, 2017
Priority date	Aug 26, 2016
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

This application relates generally to certain substituted pyrrolizine compounds, and pharmaceutical compositions which inhibit HBV replication, and methods of making and using them.

First claim

The invention claimed is:

1. A compound, which is

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , which is

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

4. The pharmaceutical composition of claim 3 , further comprising one or more additional therapeutic agents.

5. The pharmaceutical composition of claim 4 , wherein the one or more additional therapeutic agents are selected from HBV combination drugs, HBV vaccines, HBV DNA polymerase inhibitors, immunomodulators toll-like receptor (TLR) modulators, interferon alpha receptor ligands, hyaluronidase inhibitors, hepatitis b surface antigen (HBsAg) inhibitors, cytotoxic T-lymphocyte-associated protein 4 (ipi4) inhibitors, cyclophilin inhibitors, HBV viral entry inhibitors, antisense oligonucleotide targeting viral mRNA, short interfering RNAs (siRNA) and ddRNAi endonuclease modulators, ribonucelotide reductase inhibitors, HBV E antigen inhibitors, covalently closed circular DNA (cccDNA) inhibitors, farnesoid X receptor agonists, HBV antibodies, CCR2 chemokine antagonists, thymosin agonists, cytokines, nucleoprotein modulators, retinoic acid-inducible gene 1 stimulators, NOD2 stimulators, phosphatidylinositol 3-kinase (PI3K) inhibitors, indoleamine-2, 3-dioxygenase (IDO) pathway inhibitors, PD-1 inhibitors, PD-L1 inhibitors, recombinant thymosin alpha-1, bruton's tyrosine kinase (BTK) inhibitors, KDM inhibitors, HBV replication inhibitors, arginase inhibitors, and other HBV drugs.

6. The pharmaceutical composition of claim 4 , wherein the one or more additional therapeutic agents are selected from adefovir (HEPSERA®), tenofovir disoproxil fumarate (VIREAD®), tenofovir alafenamide, tenofovir, tenofovir disoproxil, tenofovir alafenamide fumarate, tenofovir alafenamide hemifumarate, entecavir (BARACLUDE®), telbivudine (TYZEKA), and lamivudine (EPIVIR-HBV®).

7. The pharmaceutical composition of claim 4 , wherein one or more additional therapeutic agents are selected from tenofovir alafenamide, tenofovir alafenamide fumarate, and tenofovir alafenamide hemifumarate.

Assignees

• Gilead Sciences Inc

Inventors

• Du Jinfa
• Kaplan Joshua A
• Kirschberg Thorsten A
• Kobayashi Tetsuya
• Lazerwith Scott E
• Lee Rick Andrew
• Medley Jonathan William
• Mitchell Michael L
• Morganelli Philip Anthony
• Pyun Hyung-Jung
• Shevick Sophia L
• Squires Neil H
• Watkins William J

Classifications

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61K31/403 Primary

  condensed with carbocyclic rings, e.g. carbazole · CPC title

• A61K31/433

  Thidiazoles · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title