Antiviral heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-12006326-B2
Application number	US-202217894412-A
Country	US
Kind code	B2
Filing date	Aug 24, 2022
Priority date	Oct 4, 2019
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:

which inhibit Human Respiratory Syncytial Virus (HRSV) or Human Metapneumovirus (HMPV) inhibitors. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HRSV or HMPV infection. The invention also relates to methods of treating an HRSV or HMPV 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:
A is selected from the group consisting of:
1) optionally substituted aryl; and
2) optionally substituted heteroaryl;

B is O;
R 1 and R 2 are each hydrogen;
Z is hydrogen;
W is
optionally substituted —C 1 -C 6 alkyl;

G is
—C(O)NR 11 R 12 ;

n is 1;
Y is O;
E is optionally substituted aryl;
R 3 is hydroxy or fluorine;
R 4 is selected from the group consisting of
optionally substituted —C 1 -C 6 alkyl and
optionally substituted —C 3 -C 8 cycloalkyl;

R 11 at each occurrence is independently selected from the group consisting of:
1) hydrogen;
2) optionally substituted —C 1 -C 8 -alkyl;
3) optionally substituted —C 3 -C 8 -cycloalkyl;
4) optionally substituted 3- to 8-membered heterocyclic;
5) optionally substituted aryl;
6) optionally substituted arylalkyl;
7) optionally substituted heteroaryl; and
8) optionally substituted heteroarylalkyl; and

R 12 at each occurrence is independently selected from the group consisting of:
1) hydrogen;
2) optionally substituted —C 1 -C 8 -alkyl;
3) optionally substituted —C 3 -C 8 -cycloalkyl;
4) optionally substituted 3- to 8-membered heterocyclic;
5) optionally substituted aryl;
6) optionally substituted arylalkyl;
7) optionally substituted heteroaryl; and
8) optionally substituted heteroarylalkyl;

alternatively, R 11 and R 12 are taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered heterocyclic ring.

2. The compound of claim 1 , wherein G is —C(O)NH 2 .

3. The compound of claim 1 , wherein E is selected from the groups set forth below:

4. The compound of claim 1 , wherein A is selected from the groups set forth below by removal of a hydrogen atom:

wherein each of these groups is optionally substituted.

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

wherein R 21 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; m is 0, 1, 2, 3, 4 or 5; and A, W, R 3 , R 4 , R 11 , and R 12 are as defined in claim 1 .

6. The compound of claim 1 , represented by Formula (X-1), or a pharmaceutically acceptable salt thereof:

wherein R 21 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; m′ is 0, 1 or 2; and A, W, R 11 , and R 12 are as defined in claim 1 .

7. The compound of claim 1 , represented by Formula (X-1a), or a pharmaceutically acceptable salt thereof:

wherein R 21 is optionally substituted methyl, halo, CN, OR 11 , or NR 11 R 12 ; m′ is 0, 1 or 2; and A, W, R 11 , and R 12 are as defined in claim 1 .

8. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

9. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 .

10. The method of claim 9 , further comprising the step of administering to the subject an anti-RSV agent.

11. The method of claim 9 , further comprising administering to the subject a steroid anti-inflammatory compound.

12. A method of treating RSV and influenza in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 and a therapeutically effective amount of an anti-influenza agent.

13. The method of claim 10 , wherein the compound and the anti-RSV agent are co-formulated.

14. The method of claim 10 , wherein the compound and the anti-RSV agent are co-administered.

15. The method of claim 10 , wherein administering the compound allows for administering of the anti-RSV agent at a lower dose or frequency as compared to the administering of the anti-RSV agent alone that is required to achieve similar results in prophylactically treating an RSV infection in a subject in need thereof.

16. A method of treating an HMPV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds of claim 1 .

17. The method of claim 16 , further comprising the step of administering to the subject an anti-HMPV agent.

18. The method of claim 17 , wherein the compound and the anti-HMPV agent are co-formulated.

Assignees

• Enanta Pharm Inc

Inventors

• Szymaniak Adam
• Mcgrath Kevin
• Yu Jianming
• Mann Tyler
• Nguyen Long
• Zhu Kaicheng
• Kim In Jong
• Or Yat Sun

Classifications

• C07D491/048 Primary

  the oxygen-containing ring being five-membered · CPC title

• C07D491/044

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D491/052 Primary

  the oxygen-containing ring being six-membered · CPC title