Granted Patent B2

US 12,509,470 · App. 18/647,107 · Granted Dec 30, 2025

Inventors: Adam Szymaniak (Boston, MA); Kevin McGrath (Brighton, MA); Jianming Yu (Plainsboro, NJ); Tyler J. Mann (Brighton, MA); Long Nguyen (Boston, MA); Kaicheng Zhu (Belmont, MA); In Jong Kim (Lexington, MA); Yat Sun Or (Waltham, MA)

Assignee: Enanta Pharmaceuticals, Inc.

C07D491/052C07D471/04C07D491/044C07D491/048

Abstract

Claims (89)

1 . A compound represented by Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is

Ra is hydrogen, halogen, —CN, —NO 2 , —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 S(O) 2 R 12 , —S(O) 2 R 12 , —S(O) 2 NR 11 R 12 , —NR 11 C(O)NR 11 R 12 , —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 3 -C 8 -cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl;

Rb and Rb′ are each independently selected from hydrogen, halogen, —OR 11 , —NR 11 R 12 , optionally substituted —C 1 -C 6 -alkyl, optionally substituted —C 3 -C 8 -cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl;

B is O or S;

R 1 and R 2 are each independently selected from the group consisting of:

1) hydrogen;

2) fluorine; and

3) optionally substituted —C 1 -C 6 alkyl;

alternatively, R 1 and R 2 are taken together with the carbon atom which they attached to form an optionally substituted 3- to 6-membered cyclic ring;

Z is selected from the group consisting of:

1) hydrogen;

2) halogen;

3) hydroxy;

4) cyano;

5) nitro;

6) optionally substituted —C 1 -C 6 alkoxy; and

7) optionally substituted —C 1 -C 6 alkyl;

W is selected from the group consisting of:

1) hydrogen;

2) halogen;

3) optionally substituted —C 1 -C 6 alkoxy;

4) optionally substituted —C 1 -C 6 alkyl; and

5) optionally substituted —C 3 -C 6 cycloalkyl;

G is selected from the group consisting of:

1) —C(O)OR 12 ;

2) —C(O)NR 11 R 12 ;

3) optionally substituted —C 1 -C 6 alkyl-CN;

4) optionally substituted —C 1 -C 6 alkyl-C(O)NR 11 R 12 ;

5) optionally substituted —C 1 -C 6 alkyl-C(O)NR 11 S(O) 2 R 12 ;

6) optionally substituted —C 1 -C 6 alkyl-OC(O)NR 11 R 12 ;

7) optionally substituted —C 1 -C 6 alkyl-NHR 13 ; and

8) optionally substituted —C 1 -C 6 alkyl-NHC(O)R 13 ;

n is 1, 2 or 3;

Y is O, S, S(O) 2 , or NR 14 ,

E is selected from the group consisting of:

1) optionally substituted aryl;

2) optionally substituted heteroaryl;

3) optionally substituted 3- to 8-membered heterocyclic, and

4) optionally substituted alkynyl;

R 3 is hydroxy or fluorine;

R 4 is selected from the group consisting of:

1) hydrogen;

2) optionally substituted —C 1 -C 6 alkyl;

3) optionally substituted —C 3 -C 8 cycloalkyl; and

4) optionally substituted 3- to 8-membered heterocyclic;

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;

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; R 13 at each occurrence is independently selected from the group consisting of:

1) Optionally substituted —C 1 -C 8 alkyl;

2) Optionally substituted —C 3 -C 8 cycloalkyl;

3) Optionally substituted 3- to 8-membered heterocyclic;

4) Optionally substituted aryl;

5) Optionally substituted arylalkyl;

6) Optionally substituted heteroaryl; and

7) Optionally substituted heteroarylalkyl; and

R 14 is selected from:

1) hydrogen;

2) optionally substituted —C 1 -C 8 -alkyl; and

3) optionally substituted —C 3 -C 8 -cycloalkyl.

2 . The compound of claim 1 , wherein A is selected from the group consisting of

3 . The compound of claim 1 , wherein E is selected from the group consisting of

4 . The compound of claim 1 , wherein G is —C(O)NR 11 R 12 .

5 . The compound of claim 1 , wherein

A is selected from the group consisting of

E is selected from the group consisting of

G is —C(O)NR 11 R 12 ;

B is O; and

n is 1.

6 . A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

7 . A method of treating a respiratory syncytial virus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .

8 . A method of treating a human metapneumovirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .

Continuity (7)

References Cited (156)