IP Library Granted Patent US 11,629,125
Granted Patent B2
US 11,629,125 · App. 16/998,944 · Granted Apr 18, 2023

Elimination of hepatitis b virus with antiviral agents

Inventors: Raymond F. Schinazi (Miami, FL); Sebastien Boucle (Smyrna, GA); Franck Amblard (Atlanta, GA); Ozkan Sari (Decatur, GA); Leda Bassit (Smyrna, GA)
Assignee: Emory University
C07D207/34A61K31/40A61K31/41A61K31/4178A61K31/4184A61K31/4192A61K31/427A61K31/454A61K31/496A61K31/506A61K31/5377A61K45/06A61P31/20C07D207/36C07D249/04C07D401/06C07D401/12C07D403/06C07D403/12C07D417/12
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 11,629,125
App. No.
16/998,944
Granted
Apr 18, 2023
Kind
B2
Abstract

The present invention is directed to compounds, compositions and methods for preventing, treating or curing Hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.

Claims (22)

1. A compound of the following formula:

or a pharmaceutically acceptable salt thereof, wherein

when R 1 and R 1′ are attached to a carbon, they are, independently, hydrogen, halogen, SF 5 , CF 3 , hydroxy, N(R′)S(O) 2 R′, S(O) 2 R′, S(O) 2 N(R′) 2 , C 1-6 alkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, cyano, C 2-6 alkynyl, C 3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C 1-6 alkyl, arylalkoxycarbonyl, carboxy, C 1-6 haloalkyl, heterocyclylalkyl, or C 1-6 hydroxyalkyl;

when R 1 and R 1′ are attached to a nitrogen, they are, independently, hydrogen, C 2-6 alkoxy, C 3-6 alkoxyalkyl, C 2-6 alkenyl, alkoxycarbonyl, carbonylalkyl, carbonyl aryl, C 1-6 alkyl, heterocyclylalkyl, C 2-6 hydroxyalkyl, or S(O) 2 R′;

each R′ is independently H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, aryl, heteroaryl, alkylaryl, or arylalkyl, or if two R′ reside on the same nitrogen atom, they can come together to form a C 3-6 ring optionally containing a N, O, or S heteroatom;

the R′ groups, other than H, can optionally be substituted with one or more substituents, which substituents are, independently, halo, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, alkoxyalkyl, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphonic acid, or phosphonate;

u and v are independently 0, 1, 2, 3, 4 or 5;

K is a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, or S; or a C 4-14 bicyclic ring;

L is a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, or S,

W is

R 14 is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl,

R 15 is C 1-6 alkyl, C 1-6 haloalkyl, C 2-8 alkoxyalkyl, a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, a seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S or Se; a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se;

R 15 is optionally substituted with one or more substituents which are, independently, halogen, SF 5 , CF 3 , hydroxy, N(R′)S(O) 2 R′, S(O) 2 R′, S(O) 2 N(R′) 2 , C 1-6 alkoxy, C 1-6 haloalkoxy, cyano, azido, C 2-6 alkynyl, C 3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C 1-6 alkyl, cycloalkyl, arylalkoxycarbonyl, carboxy, C 1-6 haloalkyl, heterocyclylalkyl, or C 1-6 hydroxyalkyl; or is optionally substituted with aryl, substituted aryl, heteroaryl, or substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF 5 , CF 3 , hydroxy, N(R′)S(O) 2 R′, S(O) 2 R′, S(O) 2 N(R′) 2 , C(O)R′, C 1-6 alkoxy, cyano, azido, C 2-6 alkynyl, C 3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C 1-6 alkyl, or

R 14 and R 15 can come together with the nitrogen to which they are attached form a 6-10 membered bicyclic or bridged ring or a 3 to 8 membered saturated ring; such bicyclic, bridged and saturated ring moiety optionally containing one or more additional heteroatoms which are, independently, O, S or N, and optionally being substituted with one or more substituents each independently selected from the group consisting of halogen, CF 3 , hydroxy, N(R′)S(O) 2 R′, S(O) 2 R′, S(O) 2 N(R′) 2 , C 1-6 alkoxy, cyano, azido, C 2-6 alkynyl, C 3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C 1-6 alkyl, arylalkoxycarbonyl, carboxy, C 1-6 haloalkyl, heterocyclylalkyl, and C 1-6 hydroxyalkyl.

2. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable carrier.

3. A method for treating a host infected with HBV, comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the host in need of treatment thereof.

4. The method of claim 3 , wherein the treating a host infected with HBV suppresses HDV infection.

5. The compound of claim 1 , wherein R 1′ is halogen or CN.

6. The compound of claim 1 , wherein R 1 is methyl.

7. The compound of claim 1 , wherein L is an optionally substituted pyrrole.

8. The compound of claim 1 , wherein K is optionally substituted pyridyl.

9. The compound of claim 1 , wherein R 14 is C 2-6 alkenyl or C 2-6 alkynyl.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2020
From: SCHINAZI, RAYMOND F.; BOUCLE, SEBASTIEN; AMBLARD, FRANCK; SARI, OZKAN; BASSIT, LEDA
To: EMORY UNIVERSITY
Reel/Frame 053556/0830 →
Continuity (3)
Continuation 16082747
Provisional Application 62305865 · Mar 9, 2016
Related Publication 20210114981A1 · Apr 22, 2021