Functionalized heterocycles as antiviral agents

Patent metadata

Field	Value
Publication number	US-11236108-B2
Application number	US-202017022660-A
Country	US
Kind code	B2
Filing date	Sep 16, 2020
Priority date	Sep 17, 2019
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, thereof:which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

First claim

What is claimed:

1. A compound represented by Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen, optionally substituted —C 1 -C 6 alkyl, or optionally substituted —C 3 -C 6 cycloalkyl;
R 2 is hydrogen, halo, CN, optionally substituted C 1 -C 6 alkyl, or optionally substituted C 1 -C 6 alkoxy;
R 3 is selected from:
1) hydrogen;
2) halogen;
3) —NO 2 ;
4) cyano;
5) optionally substituted —C 1 -C 8 alkyl;
6) optionally substituted —C 2 -C 8 alkenyl;
7) optionally substituted —C 2 -C 8 alkynyl;
8) optionally substituted —C 3 -C 8 cycloalkyl;
9) optionally substituted 3- to 8-membered heterocyclic;
10) optionally substituted aryl;
11) optionally substituted arylalkyl;
12) optionally substituted heteroaryl;
13) optionally substituted heteroarylalkyl;
14) —N(R 11 )(R 12 );
15) —OR 11 ;
16) —SR 11 ; and
17) —S(O) 2 R 11 ;
A is optionally substituted —C 3 -C 8 cycloalkenyl; optionally substituted unsaturated 3- to 8-membered heterocycloalkyl; optionally substituted aryl; optionally substituted heteroaryl;
Q is NR 12 , O, S, or SO 2 ;
R 4 and R 5 are each independently selected from hydrogen, halo, —N(R 11 )(R 12 ), optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 1 -C 6 alkoxy, optionally substituted —C 3 -C 8 cycloalkyl; optionally substituted 3- to 8-membered heterocycloalkyl; optionally substituted aryl;
and optionally substituted heteroaryl;
alternatively, R 4 and R 5 are taken together with the carbon atom to which they are attached to form an optionally substituted 3-8 membered heterocyclic or carbocyclic ring containing 0, 1, 2, or 3 double bonds;
R 6 is hydrogen or optionally substituted methyl;
W is —COOR 11 , —C(O)NHSO 2 R 11 , —C(O)NHSO 2 NR 11 R 12 , 5-tetrazolyl, or 1,2,4-oxadiazol-3-yl-5(4H)-one; and
Each R 11 and R 12 is independently selected from hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl, alternatively, R 11 and R 12 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3-8 membered heterocyclic containing 0, 1, 2, or 3 double bonds.

2. The compound of claim 1 , wherein A is optionally substituted 5- to 7-membered unsaturated heterocyclic, or optionally substituted 5- to 6-membered heteroaryl.

3. The compound of claim 1 , represented by Formula (II), or a pharmaceutically acceptable salt thereof:

wherein R 1 , R 2 , R 3 , A, Q, R 4 , R 5 , R 6 , and W are as defined in claim 1 .

4. The compound of claim 1 , represented by Formula (VI), or a pharmaceutically acceptable salt thereof:

wherein one U is —O—, —S—, or —NR 22 —, and the other Us are independently N, —NR 22 —, —C(R 21 ) 2 — or —C(R 21 )—; wherein at least one pair of adjacent Us are taken together to form —C(R 21 )═C(R 21 )—, —C(R 21 )═N—, or —N═N—; m is 0, 1, 2 or 3; each R 21 is independently hydrogen, halogen, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 2 -C 6 alkenyl, optionally substituted —C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 alkoxy; optionally substituted —C 3 -C 7 cycloalkyl, optionally substituted 3- to 7-membered heterocyclic, optionally substituted aryl or optionally substituted heteroaryl; each R 22 is independently hydrogen, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 2 -C 6 alkenyl, optionally substituted —C 2 -C 6 alkynyl, optionally substituted C 1 -C 6 alkoxy; optionally substituted —C 3 -C 7 cycloalkyl, optionally substituted 3- to 7-membered heterocyclic, optionally substituted aryl or optionally substituted heteroaryl; R 1 , R 3 , Q, R 4 , and W are as defined in claim 1 .

5. The compound of claim 1 , represented by one of Formulae (TX-1)˜(IX-6), or a pharmaceutically acceptable salt thereof:

wherein R 1 , R 3 , R 4 , and R 11 are as defined in claim 1 .

6. The compound of claim 1 , selected from the compounds set forth below or a pharmaceutically acceptable salt thereof:

Compound
Structure

1

2

3

4

5

6

1a

2a

Assignees

• Enanta Pharm Inc

Inventors

• Panarese Joseph D
• Kenton Nathaniel Thomas
• Bartlett Samuel
• Davis Dexter
• Or Yat Sun

Classifications

• C07D495/14 Primary

  Ortho-condensed systems · CPC title

• C07D491/147 Primary

  the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom · CPC title

• C07D491/153

  the condensed system containing two rings with oxygen as ring hetero atom and one ring with nitrogen as ring hetero atom · CPC title