Novel spiropyrrolidine derived antiviral agents

Patent metadata

Field	Value
Publication number	US-2023151019-A1
Application number	US-202217983501-A
Country	US
Kind code	A1
Filing date	Nov 9, 2022
Priority date	Nov 12, 2021
Publication date	May 18, 2023
Grant date	—

Abstract

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

which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

First claim

1 . A compound represented by Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:
A is selected from:
1) —R 11 ;
2) —OR 12 ; and
3) —NR 13 R 14 ;

-L 1 - is

-L 2 - is

B is an optionally substituted aryl or optionally substituted heteroaryl;
X is selected from:
1) —CN;
2) —C(O)R 15 ;
3) —CH(OH)SO 3 R 16 ;
4) —C(O)NR 13 R 14 ;
5) —C(O)C(O)NR 13 R 14 ; and
6) —C≡C—R 17 ;

R 1 , R 2 , R 3 , R 5 , R 6 , and R 17 are each independently selected from:
1) Hydrogen;
2) Optionally substituted —C 1 -C 8 alkyl;
3) Optionally substituted —C 2 -C 8 alkenyl;
4) Optionally substituted —C 2 -C 8 alkynyl;
5) Optionally substituted —C 3 -C 8 cycloalkyl;
6) Optionally substituted 3- to 8-membered heterocycloalkyl;
7) Optionally substituted aryl;
8) Optionally substituted arylalkyl;
9) Optionally substituted heteroaryl; and
10) Optionally substituted heteroarylalkyl;
alternatively, R 1 and R 2 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;
alternatively, R 2 and R 3 are taken together with the carbon atom and nitrogen atom to which they are corresponding attached to form an optionally substituted 4- to 8-membered heterocyclic ring;
alternatively, R 5 and R 6 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;

R 4 is hydrogen, optionally substituted —C 1 -C 4 alkyl, optionally substituted C 2 -C 4 -alkenyl, or optionally substituted —C 3 -C 6 cycloalkyl;
R 11 is selected from:
1) Optionally substituted —C 1 -C 8 alkyl;
2) Optionally substituted —C 2 -C 8 alkenyl;
3) Optionally substituted —C 2 -C 8 alkynyl;
4) Optionally substituted —C 3 -C 8 cycloalkyl;
5) Optionally substituted 3- to 8-membered heterocycloalkyl;
6) Optionally substituted aryl;
7) Optionally substituted arylalkyl;
8) Optionally substituted heteroaryl; and
9) Optionally substituted heteroarylalkyl;

R 12 , R 13 , and R 14 each independently selected from:
1) Hydrogen;
2) Optionally substituted —C 1 -C 8 alkyl;
3) Optionally substituted —C 2 -C 8 alkenyl;
4) Optionally substituted —C 2 -C 8 alkynyl;
5) Optionally substituted —C 3 -C 8 cycloalkyl;
6) Optionally substituted 3- to 8-membered heterocycloalkyl;
7) Optionally substituted aryl;
8) Optionally substituted arylalkyl;
9) Optionally substituted heteroaryl; and
10) Optionally substituted heteroarylalkyl;
alternatively, R 13 and R 14 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic ring;

R 15 is hydrogen, hydroxy, optionally substituted —C 1 -C 8 alkyl, or optionally substituted heteroaryl; and R 16 is hydrogen or Na + .

2 . The compound of claim 1 , wherein -L 1 - is

-L 2 - is

and X is —CN.

3 . The compound of claim 1 , wherein X is derived from one of the following by removal of a hydrogen atom, and optionally substituted:

4 . The compound of claim 1 , represented by Formulae (IV-1)˜(IV-3), or a pharmaceutically acceptable salt thereof:

wherein A, B, R 1 , R 3 , R 5 , R 6 , and X are as defined in claim 1 .

5 . The compound of claim 1 , represented by one of Formulae (XI-1) to (XI-3), or a pharmaceutically acceptable salt thereof:

wherein A, R 1 , R 3 , R 5 , R 6 , and X are as defined in claim 1 .

6 . The compound of claim 1 , represented by Formulae (XVII-1b) to (XVII-5b), or a pharmaceutically acceptable salt thereof:

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

7 . The compound of claim 1 , represented by one of Formula (XVIII-1a) to (XVIII-15a), or a pharmaceutically acceptable salt thereof:

wherein A and R 1 are as defined in claim 1 .

8 . 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

7

Assignees

• Enanta Pharm Inc

Inventors

• Cao Hui
• Li Wei
• Gao Xuri
• Zhang Jiajun
• Peng Xiaowen
• Kass Jorden
• Shen Ruichao
• Wang Guoqiang
• Or Yat Sun

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D487/10 Primary

  Spiro-condensed systems · CPC title